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Delvecchio M, Piona C, Chobot A, Cudizio L, Deeb A, Elbarbary N, Dos Santos TJ, Habeb A, ISPAD JENIOUS GROUP. Knowledge, Attitudes, and Practices in Neonatal Diabetes Mellitus Management: the JEnious-NeOnatal-DIabetes (JENODI) Survey. Diabetes Ther 2025; 16:885-897. [PMID: 40106224 PMCID: PMC12006576 DOI: 10.1007/s13300-025-01714-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Accepted: 02/17/2025] [Indexed: 03/22/2025] Open
Abstract
INTRODUCTION We aimed to explore the knowledge, attitude, and management of neonatal diabetes mellitus (NDM) among members of the International Society for Pediatric and Adolescent Diabetes (ISPAD). METHODS Members of the society were invited to complete an online questionnaire posted on the ISPAD website. RESULTS We received 108 responses from 45 different countries. Of these, 103 were involved in NDM management. 87.9% of participants would start insulin at diagnosis, and 11% would prefer sulfonylurea (SU); 54.6% would start with an insulin pump, and 80.6% would use continuous glucose monitoring. Genetic testing was suggested by 97.2% (50.9% when diagnosis occurs up to 6 months, 15.7% up to 9 months, and 30.6% up to 12 months of age), while 79.6% routinely request it in clinical practice. Of the participants, 96.3% consider genetic testing necessary to identify children who can be treated with SU, and 26.9% would try SU before testing/obtaining results. Only 37% received specific training on NDM, while 44.5% felt less confident in managing patients with NDM. Incidence in the country of practice, participant's age, years of experience in the field, number of patients registered in the clinic, and number of patients with NDM followed up were associated with differences in answers. CONCLUSIONS This survey offers the possibility of informing health providers about the awareness of different aspects of NDM management. Our results provide the opportunity to compare various aspects of diagnosis and treatment of NDM in different geographic areas. Continuous education is needed to boost physicians' confidence in managing patients with this rare form of diabetes.
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Affiliation(s)
- Maurizio Delvecchio
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
| | - Claudia Piona
- Pediatric Diabetes and Metabolic Disorders Unit, Regional Center for Pediatric Diabetes, University City Hospital, Verona, Italy
| | - Agata Chobot
- Department of Pediatrics, Institute of Medical Sciences, University of Opole, Opole, Poland
- Department of Pediatrics, University Clinical Hospital in Opole, Opole, Poland
| | | | - Asma Deeb
- Faculty of Health and Science, Endocrine Division, Sheikh Shakhbout Medical City, Faculty of Medicine, Khalifa University, Ain Shams University, Abu Dhabi, United Arab Emirates
| | - Nancy Elbarbary
- Diabetes Unit, Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Tiago J Dos Santos
- Instituto Hispalense de Pediatría, Almeria, Andalusia, Spain
- Department of Nursing Sciences, Physiotherapy, and Medicine, Faculty of Health Sciences, University of Almeria, Almeria, Spain
| | - Abdelhadi Habeb
- Pediatric Department, Prince Moh bin Abdulaziz Hospital, National Guard Health Affairs, Madinah, Kingdom of Saudi Arabia
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Alzwaihri AS, Almasoudi EA, Hadrawi MT, Danish EY, Alasmari FF, Ahmed HA. Incidence and risk factors of ocular complications among patients with homocystinuria in Saudi Arabia: a cross-sectional study. Ann Med Surg (Lond) 2025; 87:2602-2607. [PMID: 40337434 PMCID: PMC12055052 DOI: 10.1097/ms9.0000000000003001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Accepted: 01/22/2025] [Indexed: 05/09/2025] Open
Abstract
Background Cysteine β-synthase deficiency, often known as classic homocystinuria, is an uncommon inborn mistake in methionine metabolism. Developmental delay, intellectual incapacity, skeletal and vascular symptoms, and ocular abnormalities are possible main clinical characteristics. Objective This study sought to describe the ocular anomalies that King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia, homocystinuria patients presented with between 2018 and 2022. Methods This retrospective research included six homocystinuria patients. Demographic and clinical characteristics of patients as age, gender, and comorbidities were collected. Relevant clinical and ophthalmic assessments, like visual acuity, fundus examination findings, complications, and type of surgery were also reported. Results Six patients with homocystinuria (12 eyes) were included. Associated diseases were mostly mental retardation (100%), epilepsy (66.7%), developmental delay (50.0%), scoliosis (33.3%), bronchiectasis (16.7%), thrombophilia (16.7%), metabolic disorders (16.7%), and deep venous thrombosis (16.7%). All patients had ectopia lentis (100%), while one patient (16.7%) had eye ectropion, one patient (16.7%) had anterior uveitis, and one patient (16.7%) had scleromalacia. Surgery type was mostly lensectomy and vitrectomy (83.3%) then scleral fixation (16.7%), and Grice green procedure (16.7%). There were insignificant differences between first and last Autoref readings in spherical, cylinder, and axis errors of right and left eyes. Conclusions Late-diagnosed homocystinuria patients frequently have abnormalities of the eyes. Ectopia lentis should always raise the possibility that homocystinuria is the cause of the condition.
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Affiliation(s)
| | | | - Manal Taha Hadrawi
- Pediatric Ophthalmology and Strabismology, Department of Ophthalmology, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
| | - Enam Y. Danish
- Pediatric Ophthalmology and Strabismology, Department of Ophthalmology, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
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El Goundali K, Chebabe M, Elkhoudri N, Hilali A. Influence of Consanguinity on Non-communicable Diseases in Settat, Morocco: Exploring Susceptibility to Chronic and Complex Health Conditions. J Res Health Sci 2025; 25:e00646. [PMID: 40259649 PMCID: PMC12009485 DOI: 10.34172/jrhs.2025.181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Revised: 12/24/2024] [Accepted: 01/24/2025] [Indexed: 04/23/2025] Open
Abstract
BACKGROUND The prevalence of non-communicable diseases (NCDs) represents a significant global health challenge, accounting for 71% of global deaths. This concern is also widespread in Morocco. Consanguinity, common in Arab and Muslim regions, could influence the genetic predisposition to these diseases. This study aimed to explore the impact of consanguineous marriage (CM) on predisposition to these chronic illnesses among the populace in Settat province, Morocco, concerning prevalent NCDs. Study Design: A cross-sectional study. METHODS This study was conducted in Settat, Morocco, from April to October 2021 and included 453 married women aged 18 and above. Participants were selected from rural and urban health centers using a two-stage sampling method. The data were collected through structured interviews using a validated questionnaire. Statistical analyses with SPSS 26 assessed associations between consanguinity and NCDs in respondents and their descendants using odds ratios (ORs) and 95% confidence intervals. RESULTS The participants had a mean age of 38.04 years, with 35% residing in rural areas and 26.7% having a CM. The results indicated that individuals with consanguineous ancestors have a greater risk of contracting NCDs, such as cardiovascular diseases (CVDs) (OR=2.047, P=0.005), diabetes (OR=1.988, P=0.009), asthma (OR=2.069, P=0.036), chronic kidney disease (CKD) (OR=1.732, P=0.045), and cancer (OR=1.646, P=0.1), compared to those with non-consanguineous parents. CONCLUSION It is essential to integrate the harmful effects of consanguinity on future generations' health into public health policy through genetic counseling, testing, screening, and awareness programs.
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Affiliation(s)
- Khaddouj El Goundali
- Laboratory of Health Sciences and Technologies, Settat, Morocco
- Higher Institute of Health Sciences, Hassan First University of Settat, Settat, Morocco
| | - Milouda Chebabe
- Higher Institute of Health Sciences, Hassan First University of Settat, Settat, Morocco
| | - Noureddine Elkhoudri
- Higher Institute of Health Sciences, Hassan First University of Settat, Settat, Morocco
| | - Abderraouf Hilali
- Higher Institute of Health Sciences, Hassan First University of Settat, Settat, Morocco
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Mushtaq N, Bashir F, Zahid S, Riaz Q, Javed G, Tariq M, Qureshi BM, Hilal K, Ramaswamy V, Hawkins C, Minhas K, Bouffet E. Medulloblastoma Molecular Subgrouping and Outcomes Data of a Single Center From a Low- and Middle-Income Country. Pediatr Blood Cancer 2025; 72:e31555. [PMID: 39835690 DOI: 10.1002/pbc.31555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 12/03/2024] [Accepted: 01/07/2025] [Indexed: 01/22/2025]
Abstract
INTRODUCTION Medulloblastoma (MB) is the most common malignant childhood brain tumor. Molecular subgrouping of MB has become a major determinant of management in high-income countries. Subgrouping is still very limited in low- and middle-income countries (LMICs), and its relevance to management with the incorporation of risk stratification (low risk, standard risk, high risk, and very high risk) has yet to be evaluated in this setting. We describe molecular findings from a tertiary care center in Pakistan and their implications for outcome. METHODS Children aged between 3 and 18 years diagnosed with MB from April 2014 to December 2020 at Aga Khan University Hospital (AKUH) were included. Subgrouping was performed by NanoString through a collaboration with The Hospital for Sick Children, Toronto. RESULTS Thirty-seven patients (30 males) were included in this study; median age was 9 years. Twenty patients (54.1%) were high-risk, including 12 with metastatic disease. In 30 children, there was a clear molecular subgroup: 4 wingless (WNT) (10.8%), 6 sonic hedgehog (SHH) (16.2%), 3 Group 3 (8.1%), and 17 Group 4 (45.9%) MBs. Molecular subgrouping was inconclusive for three patients (8.1%) and not done in four patients (10.8%). All patients underwent surgery; 26 patients received radiation therapy at AKUH, and 9 were referred outside for radiotherapy; 24 patients received chemotherapy at AKUH (10 outside AKUH). Overall survival (OS) at 5 years was 100%, 66.7%, 66.7%, and 88.2% for WNT, SHH, Group 3, and Group 4 patients, respectively (p = 0.668). Low- and standard-risk patients had a 5-year OS of 100%, whereas very high-risk patients exhibited a significantly lower OS of 0% (p < 0.001). CONCLUSION WNT and Group 4 patients had excellent results despite one WNT patient having metastatic disease and eight Group 4 patients being high risk. Our study depicts that molecular subgrouping aids in accurately predicting survival, suggesting the potential benefit of tailored testing and treatment in the LMIC setting.
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Affiliation(s)
- Naureen Mushtaq
- Department of Oncology, Aga Khan University Hospital, Karachi, Pakistan
| | - Farrah Bashir
- Department of Oncology, Aga Khan University Hospital, Karachi, Pakistan
| | - Soha Zahid
- Department of Oncology, Aga Khan University Hospital, Karachi, Pakistan
| | - Quratulain Riaz
- Department of Pediatric Oncology, Indus Hospital, Karachi, Pakistan
| | - Gohar Javed
- Department of Surgery, Aga Khan University Hospital, Karachi, Pakistan
| | - Maria Tariq
- Department of Oncology, Radiation Oncology Section, the Aga Khan University Hospital, Karachi, Pakistan
| | - Bilal Mazhar Qureshi
- Department of Oncology, Radiation Oncology Section, the Aga Khan University Hospital, Karachi, Pakistan
| | - Kiran Hilal
- Department of Radiology, Aga Khan University Hospital, Karachi, Pakistan
| | - Vijay Ramaswamy
- The Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Cynthia Hawkins
- Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Canada
| | - Khurram Minhas
- Department of Pathology and Laboratory Medicine, Aga Khan University Hospital Karachi, Karachi, Pakistan
| | - Eric Bouffet
- The Hospital for Sick Children, University of Toronto, Toronto, Canada
- Global Neuro-Oncology Program, Department of Global Pediatric Medicine, Saint Jude Children's Research Hospital, Memphis, USA
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Subramanian S. The Abundance of Harmful Rare Homozygous Variants in Children of Consanguineous Parents. BIOLOGY 2025; 14:310. [PMID: 40136566 PMCID: PMC11940780 DOI: 10.3390/biology14030310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 03/16/2025] [Accepted: 03/17/2025] [Indexed: 03/27/2025]
Abstract
The children born of consanguineous union were found to have a higher incidence of recessive genetic diseases than the offspring of unrelated parents. The reason for this was predicted to be the presence of more deleterious rare homozygous genetic variants in the former compared to the latter. However, the magnitude of this difference is unknown. Using more than 2500 whole genomes, we show here that the individuals born of the union between double (paternal and maternal) first cousins had 20 times more deleterious rare homozygous single nucleotide variants (SNVs) than those who had unrelated parents. Furthermore, the children of first cousins had 10 times, and the children of second cousins had two times more of these SNVs compared to those present in the offspring of unrelated parents. Similar magnitudes of differences were found for the nonsynonymous deleterious rare homozygous SNVs (19, 10, and 2 times, respectively). In contrast, the differences in the number of deleterious low-frequency and common homozygous variants between the children of cousins and those of unrelated parents were 1-3 times and 1-7%, respectively. These results suggest that the offspring of consanguineous union could have a 20 times higher risk of recessive autosomal diseases caused by rare variants. Conversely, consanguinity appears to have little effect on the risk of common diseases. These findings have implications for future clinical research in identifying genetic variants associated with inherited diseases. Furthermore, the magnitude of the elevated risk revealed in this study could be useful in genetic counseling and for public health in creating awareness.
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Affiliation(s)
- Sankar Subramanian
- Centre for Bioinnovation, School of Science, Technology, and Engineering, The University of the Sunshine Coast, Moreton Bay, QLD 4502, Australia
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Hanna EM, Mehawej C, Assy J, Corbani S, Korban R, Megarbane A, Chouery E. Predicting Consanguinity Rates from Exome Sequencing Data in the Lebanese Population. J Mol Diagn 2025; 27:177-183. [PMID: 39725013 DOI: 10.1016/j.jmoldx.2024.11.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 10/11/2024] [Accepted: 11/26/2024] [Indexed: 12/28/2024] Open
Abstract
Consanguinity, prevalent in certain populations because of cultural and social factors, significantly increases the risk of genetic autosomal recessive disorders. In Lebanon, consanguineous marriages constitute 35.5% of unions, with first cousin marriages being the most common. This study aims to develop a model to predict consanguinity status using total runs of homozygosity (ROH) size derived from exome sequencing data. In this study, a cohort of 784 Lebanese individuals was analyzed, with consanguinity labels assigned based on pedigree information. ROHs were detected from exome sequencing data using AutoMap. The analysis focused on 521 subjects for whom the consanguinity or nonconsanguinity label was clearly determined, leading to the development of two logistic regression models: one including outliers (accuracy, 91%) and one excluding them (accuracy, 94%). The second model established specific ROH thresholds for categorizing consanguinity: nonconsanguineous [<40.28 megabases (Mb)], uncertain (40.28 to 79.17 Mb), probable consanguinity (79.18 to 118.06 Mb), and consanguineous (>118.06 Mb). This study provides a valuable tool for clinical genetics in populations with high consanguinity rates, offering insights into the genetic risks associated with consanguinity and aiding in the identification and counseling of affected individuals. Moreover, the current findings underline the importance of population-specific thresholds in accurately assessing consanguinity status.
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Affiliation(s)
- Eileen Marie Hanna
- Department of Computer Science and Mathematics, Lebanese American University, Byblos, Lebanon
| | - Cybel Mehawej
- Department of Human Genetics, Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos, Lebanon
| | - Joelle Assy
- Department of Computer Science and Mathematics, Lebanese American University, Byblos, Lebanon
| | - Sandra Corbani
- Department of Human Genetics, Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos, Lebanon
| | - Rima Korban
- Department of Human Genetics, Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos, Lebanon
| | - Andre Megarbane
- Department of Human Genetics, Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos, Lebanon; Institut Jérôme Lejeune, Paris, France.
| | - Eliane Chouery
- Department of Human Genetics, Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos, Lebanon.
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Rashid ZA, Mashige KP, Moodley VR. Prevalence and demographic profile of keratoconus among high school students in Kenya. Int Ophthalmol 2025; 45:21. [PMID: 39779526 PMCID: PMC11711645 DOI: 10.1007/s10792-024-03370-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 11/29/2024] [Indexed: 01/11/2025]
Abstract
PURPOSE To determine the prevalence and demographic profile of keratoconus (KC) among high school students in Nairobi County, Kenya. METHODS In this population-based, prospective, cross-sectional study, multistage cluster sampling was used to select the participants. All students underwent visual acuity measurement, auto-refraction, retinoscopy and corneal topography. Students with a scissors reflex on retinoscopy or corneal topography patterns suspicious of KC were referred for corneal tomography. RESULTS A total of 3051 students from 29 schools, with a mean age of 17.4 ± 1.6 years (range: 13-25 years) were screened. The prevalence of KC was 1.7% (n = 51) (95% CI, 1.2-2.2) and of KC suspects was 3.8% (n = 117) (95% CI, 3.2-4.6). There were no significant associations between the prevalence of KC and gender, age or ethnicity (all p > 0.05). In the KC group, 88.2% (n = 45) were unaware of their condition, 52.9% (n = 27) were treated for allergic conjunctivitis, 45.1% (n = 23) required spectacles, 11.8% (n = 6) were recommended contact lenses in at least one eye and 49.0% (n = 25) were recommended corneal cross-linking. CONCLUSIONS Among adolescents, the results of this study indicate a higher prevalence of KC compared to that reported in South Korea, Norway, Brazil and Caucasians in New Zealand, but less than that reported in some countries in the Middle East. Given the high prevalence revealed in this study, a national school screening program and clinical guidelines for screening, diagnosis and management of KC is recommended.
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Affiliation(s)
- Zahra Aly Rashid
- Discipline of Optometry, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
| | | | - Vanessa Raquel Moodley
- Discipline of Optometry, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
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Yousef NA, ElHarouni AA, Shaik NA, Banaganapalli B, Al Ghamdi AF, Galal AH, Alahmadi TS, Shuaib T, Aljeaid D, Alshaer DS, Almutadares M, Elango R. Nationwide survey on awareness of consanguinity and genetic diseases in Saudi Arabia: challenges and potential solutions to reduce the national healthcare burden. Hum Genomics 2024; 18:138. [PMID: 39695766 DOI: 10.1186/s40246-024-00700-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Accepted: 11/21/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND Consanguineous marriage is a major contributing factor for many genetic diseases and a burden to the healthcare system and national economy due to costly long-term care. Earlier studies highlighted the significantly limited awareness of the higher prevalence of genetic disease due to consanguinity even among the educated Arabs. In Saudi Arabia, more than 50% of marriages are between first cousins. This national study aims to gauge the level of the public awareness regarding the consanguinity and its impact on prevalence of genetic diseases across the Saudi Arabia. METHODS A cross-sectional bilingual online survey was conducted across Saudi Arabia, distributed through a variety of social media platforms for all residents. Pooled summary data was used from the participants. RESULTS Majority of the 9191 participants are < 30 years of age (72.85%), single (61.35%), women (74.12%) and college educated (77.16%). Consanguineous marriages are common in the extended family of 61.24% of participants. Though majority of them (85.45%) recognise the higher genetic disease risk associated with consanguinity, low awareness among men was observed (76.61 vs 88.53%). Sickle cell anaemia and thalassemia were not considered as genetic diseases by 60.68% of males and 48.39% of females, though they are the most common genetic diseases in Saudi Arabia. More women are aware of the carrier screening tests than men (42.62 vs 34.56%). Only 6.87% know the rationale behind the national mandatory premarital screening tests and the diseases screened. Although almost all (99.18%) are active users of the social media, 47.77% of men and 57.17% of women use them to search for health-related information. CONCLUSION The present study, one of the largest national surveys in highly consanguineous society, highlights that even the young and college-educated participants have low awareness of the genetic disease burden, which is strikingly high in all corners of the country. Social media platforms can be used by genetic professionals and national organizations to disseminate the reliable educational material to the public to reduce the national healthcare and economic burden in the future.
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Affiliation(s)
- Nura A Yousef
- Genetic Medicine Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- Princess Al-Jawhara Centre of Excellence in Research of Hereditary Disorders (PACER-HD), Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- Molecular Biology Department, Northern Borders Regional Laboratory, Arar, Saudi Arabia
| | - Ashraf A ElHarouni
- Genetic Medicine Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- Genetic Medicine Department, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
| | - Noor Ahmad Shaik
- Genetic Medicine Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- Princess Al-Jawhara Centre of Excellence in Research of Hereditary Disorders (PACER-HD), Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Babajan Banaganapalli
- Genetic Medicine Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- Princess Al-Jawhara Centre of Excellence in Research of Hereditary Disorders (PACER-HD), Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | | | - Amani H Galal
- Ophthalmogenetics Department, Research Institute of Ophthalmology, Cairo, Egypt
| | | | - Taghreed Shuaib
- Princess Al-Jawhara Centre of Excellence in Research of Hereditary Disorders (PACER-HD), Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- Pediatrics Department, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Deema Aljeaid
- Genetic Medicine Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- Genetic Medicine Department, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
| | - Dalal S Alshaer
- Genetic Medicine Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- Genetic Medicine Department, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
| | - Mahmoud Almutadares
- Genetic Medicine Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
- Genetic Medicine Department, King Abdulaziz University Hospital, Jeddah, Saudi Arabia.
| | - Ramu Elango
- Genetic Medicine Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
- Princess Al-Jawhara Centre of Excellence in Research of Hereditary Disorders (PACER-HD), Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
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Sasi AP, Udgiri R, Ganganahalli P, Sorganvi VM. Sociodemographic Factors and Awareness of Consanguineous Marriages in Rural Northern Karnataka: A Cross-Sectional Study. Cureus 2024; 16:e76376. [PMID: 39867089 PMCID: PMC11759663 DOI: 10.7759/cureus.76376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 12/25/2024] [Indexed: 01/28/2025] Open
Abstract
Background Consanguineous marriages, defined as unions between closely related individuals, are influenced by a complex interplay of cultural, social, economic, religious, and demographic factors. These marriages are prevalent among communities such as Hindus, Muslims, Jews, Buddhists, Christians, and Parsis in Southern and Western Asia, with significant regional variations within India. There is a lack of appropriate decision-making among women in consanguineous unions, particularly those with a low level of educational attainment, which leads to an increase in the prevalence of consanguineous marriages. This needs to be addressed through more studies and educational campaigns. Therefore, the primary objective of this study is to assess knowledge about the consequences of consanguinity and the sociodemographic factors related to consanguinity. Methodology A cross-sectional study was conducted in Unnat Bharat Abhiyan villages (Ukkali, Donur, Yambatnal, Hegadihal, Deginal) enrolled under Shri B. M. Patil Medical College, Hospital and Research Centre, BLDE (Deemed to be University), Vijayapura, India, which was selected using a lottery method. The houses were selected randomly, focusing on ever-married females aged 15-49 within the reproductive age group. Data on sociodemographic profile, marital status, and awareness status of the participants were collected from March 2023 to April 2024 using an interview technique with a pretested, semi-structured questionnaire. Results The study involved the enrollment of a total of 108 participants (Donur - 24, Yembatnal - 32, Ukkali - 27, Deginal - 10, Hegadihal - 15). Among the respondents, only 37 participants (34%) know the specific health and genetic consequences of consanguinity, such as increased risk of genetic disorders (stillbirth, milestone delay, cerebral palsy). The study highlights a significant association between respondents' knowledge of the consequences of consanguineous marriage, their literacy level, and socioeconomic status. Conclusion The study concludes that literacy levels are inversely related to the prevalence of consanguineous marriages, suggesting that education holds the key to reducing this practice. The results of this study highlight the necessity of tackling this problem through a multifaceted strategy. This strategy should include culturally sensitive educational programs, economic empowerment initiatives for women, and religious discourse that promotes genetic diversity, offering the potential for change and progress.
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Affiliation(s)
- Arun P Sasi
- Community Medicine, Shri. B. M. Patil Medical College, Hospital and Research Centre, BLDE (Deemed to be University), Vijayapura, IND
| | - Rekha Udgiri
- Community Medicine, Shri. B. M. Patil Medical College, Hospital and Research Centre, BLDE (Deemed to be University), Vijayapura, IND
| | - Praveen Ganganahalli
- Community Medicine, Shri. B. M. Patil Medical College, Hospital and Research Centre, BLDE (Deemed to be University), Vijayapura, IND
| | - Vijaya M Sorganvi
- Community Medicine, Shri. B. M. Patil Medical College, Hospital and Research Centre, BLDE (Deemed to be University), Vijayapura, IND
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Alshamlani LK, Alsulaim DS, Alabbad RS, Alhoshan AA, Alkhoder JF, Alsaleh NS, Almannai M, Ababneh F, Algattan M, Alsini L, Alswaid AF, Eyaid WM, Al Mutairi F, Umair M, Alfadhel M. Consanguinity and Occurrence of Monogenic Diseases in a Single Tertiary Centre in Riyadh, Saudi Arabia: A 2 Years Cross-Sectional Study. Appl Clin Genet 2024; 17:151-158. [PMID: 39377010 PMCID: PMC11457763 DOI: 10.2147/tacg.s476350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 08/16/2024] [Indexed: 10/09/2024] Open
Abstract
Background Consanguinity, or the practice of marrying close relatives, is a common cultural tradition in Saudi Arabia, with rates among the highest in the world. This practice has significant implications for the prevalence and distribution of major single genetic defects and chromosomal abnormalities within the Saudi population. Methods Herein, using the BESTCare electronic medical record system (designed to streamline hospital operations, enhance patient care, and improve the overall efficiency of healthcare services; bestcare.ezcaretech.com) in a single tertiary centre, King Abdullah Specialized Children Hospital (KASCH) in Riyadh, Saudi Arabia, we performed a cross-sectional study for all patients referred to the hospital from the 1st January 2020 until 1st January 2022. Results The present study, which included 1100 individuals, found a high prevalence of consanguinity (64%) and a significant proportion of third-degree relatives (69%). The mean age of participants was 12.24 years, and the diagnostic rate using advanced molecular genetics techniques was 45%, with whole exome sequencing (WES) being the most common method (43%). The study also noted a significant delay in diagnosis for more than a year in 16% of cases, with a common neurodevelopmental phenotype (18%). Conclusion In conclusion, we revealed the prevalence of consanguineous marriages in the KASCH hospital in Riyadh, Saudi Arabia. We also highlighted the most frequently referred phenotype. These findings are consistent with previous research on the prevalence and impact of consanguinity on rare genetic disorders.
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Affiliation(s)
- Lamia K Alshamlani
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
| | - Dana S Alsulaim
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
| | - Raghad S Alabbad
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
| | - Ahad A Alhoshan
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
| | - Joud F Alkhoder
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
| | - Norah S Alsaleh
- Genetics and Precision Medicine Department (GPM), King Abdullah Specialized Children Hospital (KASCH), King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
| | - Mohammed Almannai
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
- Genetics and Precision Medicine Department (GPM), King Abdullah Specialized Children Hospital (KASCH), King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
- Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNGH), Riyadh, Saudi Arabia
| | - Faroug Ababneh
- Genetics and Precision Medicine Department (GPM), King Abdullah Specialized Children Hospital (KASCH), King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
| | - Manal Algattan
- Pathology and Laboratory Medicine Department, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Lojain Alsini
- Pathology and Laboratory Medicine Department, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Abdulrahman Faiz Alswaid
- Genetics and Precision Medicine Department (GPM), King Abdullah Specialized Children Hospital (KASCH), King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
| | - Wafaa M Eyaid
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
- Genetics and Precision Medicine Department (GPM), King Abdullah Specialized Children Hospital (KASCH), King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
- Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNGH), Riyadh, Saudi Arabia
| | - Fuad Al Mutairi
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
- Genetics and Precision Medicine Department (GPM), King Abdullah Specialized Children Hospital (KASCH), King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
- Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNGH), Riyadh, Saudi Arabia
| | - Muhammad Umair
- Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNGH), Riyadh, Saudi Arabia
| | - Majid Alfadhel
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
- Genetics and Precision Medicine Department (GPM), King Abdullah Specialized Children Hospital (KASCH), King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
- Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNGH), Riyadh, Saudi Arabia
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11
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Bashiri FA, Hundallah K, Abukhaled M, Alyahya MM, Al Futaisi A, Alshowaeir D, Al Tawari A, Abdullah S, Maaz AUR, AlShamsi ET, Alshuaibi W, Alotaibi F, Aldhalaan H. Diagnosis and management of neurofibromatosis type 1 in Arabian Gulf Cooperation Council Region: challenges and recommendations. Front Oncol 2024; 14:1323176. [PMID: 39257551 PMCID: PMC11385870 DOI: 10.3389/fonc.2024.1323176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 08/05/2024] [Indexed: 09/12/2024] Open
Abstract
Neurofibromatosis type 1 (NF1) is a complex multisystem genetic disorder that requires long-term, age-specific monitoring and multidisciplinary care. NF1 symptom burden can significantly affect the quality of life and impose a substantial economic burden on patients and their families. The approval and widespread availability of mitogen-activated protein kinase (MEK) inhibitors such as selumetinib for NF1-related plexiform neurofibromas have revolutionized the standard of care for patients with NF1, however their effective utilization hinges on early recognition of NF1. We present a consensus manuscript describing the challenges observed in the Arabian Gulf Cooperation Council (GCC) for diagnosing and managing NF1. Experts from the GCC also present recommendations for the early recognition and management of NF1 and its complications. A referral pathway that can play a crucial role in helping primary healthcare providers refer their patients to experts is also proposed. Increasing the availability and accessibility of genetic testing at an affordable cost and optimizing personalized NF1 care are essential for NF1 management. Developing regional guidelines for NF1 management and establishing NF1 centers of excellence may facilitate better care and outcomes for patients with NF1 in the GCC region.
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Affiliation(s)
- Fahad A. Bashiri
- Division of Pediatric Neurology, Department of Pediatrics, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | | | - Musaad Abukhaled
- Neuroscience Centre, King Faisal Specialist Hospital and Research Centre, College of Medicine, Al Faisal University, Riyadh, Saudi Arabia
| | - Mossaed Mohammed Alyahya
- Consultant of Neuro-oncology and Neuromuscular-neurology, Department of Oncology, King Faisal Specialist Hospital and Research Centre, Department of Neuroscience, King Faisal Specialist Hospital and Research Centre, Al Faisal University, Riyadh, Saudi Arabia
| | - Amna Al Futaisi
- Sultan Qaboos University, College of Medicine and Health Sciences, Muscat, Oman
| | - Daniah Alshowaeir
- Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Asmaa Al Tawari
- Pediatric Neurology Unit, Pediatric Department, AlSabah Hospital, Ministry of Health, Kuwait City, Kuwait
| | - Shaker Abdullah
- Department of Oncology, King Faisal Specialist Hospital & Research Center – Jeddah (KFSHRC-Jed), Jeddah, Saudi Arabia
| | - Ata Ur Rehman Maaz
- HemOnc Division, Department of Child Health, Sidra Medicine, Doha, Qatar
| | - Eman Taryam AlShamsi
- Pediatric Hematology-Oncology Department, Al Jalila children’s specialty Hospital, Dubai, United Arab Emirates
| | - Walaa Alshuaibi
- Division of Medical Genetics, Department of Pediatrics, King Khalid University Hospital, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Faisal Alotaibi
- Neuroscience Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Hesham Aldhalaan
- Department of Neurosciences, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
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12
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Liscovitch-Brauer N, Mesika R, Rabinowitz T, Volkov H, Grad M, Matar RT, Basel-Salmon L, Tadmor O, Beker A, Shomron N. Machine learning-enhanced noninvasive prenatal testing of monogenic disorders. Prenat Diagn 2024; 44:1024-1032. [PMID: 38687007 DOI: 10.1002/pd.6570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 03/26/2024] [Accepted: 03/28/2024] [Indexed: 05/02/2024]
Abstract
OBJECTIVE Single-nucleotide variants (SNVs) are of great significance in prenatal diagnosis as they are the leading cause of inherited single-gene disorders (SGDs). Identifying SNVs in a non-invasive prenatal screening (NIPS) scenario is particularly challenging for maternally inherited SNVs. We present an improved method to predict inherited SNVs from maternal or paternal origin in a genome-wide manner. METHODS We performed SNV-NIPS based on the combination of fragments of cell free DNA (cfDNA) features, Bayesian inference and a machine-learning (ML) prediction refinement step using random forest (RF) classifiers trained on millions of non-pathogenic variants. We next evaluate the real-world performance of our refined method in a clinical setting by testing our models on 16 families with singleton pregnancies and varying fetal fraction (FF) levels, and validate the results over millions of inherited variants in each fetus. RESULTS The average area under the ROC curve (AUC) values are 0.996 over all families for paternally inherited variants, 0.81 for the challenging maternally inherited variants, 0.86 for homozygous biallelic variants and 0.95 for compound heterozygous variants. Discriminative AUCs were achieved even in families with a low FF. We further investigate the performance of our method in correctly predicting SNVs in coding regions of clinically relevant genes and demonstrate significantly improved AUCs in these regions. Finally, we focus on the pathogenic variants in our cohort and show that our method correctly predicts if the fetus is unaffected or affected in all (10/10, 100%) of the families containing a pathogenic SNV. CONCLUSIONS Overall, we demonstrate our ability to perform genome-wide NIPS for maternal and homozygous biallelic variants and showcase the utility of our method in a clinical setting.
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Affiliation(s)
| | | | - Tom Rabinowitz
- Identifai-Genetics Ltd., Tel Aviv, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Hadas Volkov
- Identifai-Genetics Ltd., Tel Aviv, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Edmond J Safra Center for Bioinformatics, Tel Aviv University, Tel Aviv, Israel
| | - Meitar Grad
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Reut Tomashov Matar
- Raphael Recanati Genetic Institute, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel
| | - Lina Basel-Salmon
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Raphael Recanati Genetic Institute, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel
- Felsenstein Medical Research Center, Tel-Aviv University, Tel-Aviv, Israel
| | | | - Amir Beker
- Identifai-Genetics Ltd., Tel Aviv, Israel
| | - Noam Shomron
- Identifai-Genetics Ltd., Tel Aviv, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Edmond J Safra Center for Bioinformatics, Tel Aviv University, Tel Aviv, Israel
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13
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Elmugadam FM, Ahmed H, KARAMELGHANI MOHAMMED, Ali A, Ali I, Ahmed A, Salman M, Mohamed W, Ahmed EA, Abbasher Hussien Mohamed Ahmed K, Mustafa Ahmed GE, Elsayed L, Musa A. Awareness of consanguineous marriage burden and willingness towards premarital genetic testing in Sudan: a national cross-sectional study. Ann Med Surg (Lond) 2024; 86:3959-3971. [PMID: 38989216 PMCID: PMC11230780 DOI: 10.1097/ms9.0000000000002210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Accepted: 05/14/2024] [Indexed: 07/12/2024] Open
Abstract
Background Despite the widespread practice of consanguinity in Sudan, there is a lack of exploration into the community's awareness of its health implications on offspring and their overall attitude towards consanguineous unions. Aim This study aimed to evaluate the community's awareness of the possible health adversities of consanguinity on children and assess the effect of knowledge level on the prevailing attitude towards this practice in Sudan. Methods From August to December 2018, data were collected from adults aged 18 years and above in five provinces of Sudan regardless of their marital status. The analysis involved both descriptive and multivariate statistical techniques. Results This study revealed a consanguinity rate of 30.2%. Despite a high awareness level (73.7%) regarding the effects of consanguineous marriage on the health of the offspring, a moderately negative attitude towards this practice (63.9%) was observed. Conclusion The discordance between the high consanguinity rate in the Sudanese population and the moderately negative attitude suggests a potential persistence of this practice in the future. Without the implementation of educational programs and the provision of genetic counselling services to consanguineous couples, the prevalence of consanguinity is likely to endure.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Liena Elsayed
- Department of Basic Sciences, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Ahmed Musa
- Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan
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14
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Shebani A, Mustafa AM, Elshwekh H, Hmmier A, Alhudiri IM. Knowledge and Attitudes Toward Premarital Screening Programs Among Students at the University of Tripoli, Libya. Cureus 2024; 16:e64274. [PMID: 39130983 PMCID: PMC11315591 DOI: 10.7759/cureus.64274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/10/2024] [Indexed: 08/13/2024] Open
Abstract
BACKGROUND Despite the increase in hereditary disease in Arab countries due to the high rates of consanguineous marriages, research on community awareness of premarital screening (PMS) for disease carriers is still scarce. AIM To investigate knowledge and attitudes toward genetic PMS programs among university students in Libya. METHODS A cross-sectional study was conducted using a self-administered questionnaire distributed to 421 Libyan students aged 18-25 years at the University of Tripoli. RESULTS Most of the participants (79%, n=316) agreed that a PMS program is important and expressed willingness to have PMS programs if they were advised to do so. Two-thirds of participants (67%, n=268) had heard of PMS programs, of whom (27.2%, n=73) heard of them from social media. CONCLUSION Most of the university students had good knowledge of PMS but poor knowledge of the hereditary disease targeted by PMS. Most of them had a positive attitude toward PMS.
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Affiliation(s)
- Afaf Shebani
- Genetic Engineering, Libyan Biotechnology Research Center, Tripoli, LBY
| | - Ariej M Mustafa
- Genetic Engineering, Libyan Biotechnology Research Center, Tripoli, LBY
| | - Halla Elshwekh
- Genetic Engineering, Libyan Biotechnology Research Center, Tripoli, LBY
| | - Abduladim Hmmier
- Genetic Engineering, Libyan Biotechnology Research Center, Tripoli, LBY
| | - Inas M Alhudiri
- Genetic Engineering, Libyan Biotechnology Research Center, Tripoli, LBY
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15
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Al Yaarubi S, Alsagheir A, Al Shidhani A, Alzelaye S, Alghazir N, Brema I, Alsaffar H, Al Dubayee M, Alshahrani A, Abdelmeguid Y, Omar OM, Attia N, Al Amiri E, Al Jubeh J, Algethami A, Alkhayyat H, Haleem A, Al Yahyaei M, Khochtali I, Babli S, Nugud A, Thalange N, Albalushi S, Hergli N, Deeb A, Alfadhel M. Analysis of disease characteristics of a large patient cohort with congenital generalized lipodystrophy from the Middle East and North Africa. Orphanet J Rare Dis 2024; 19:118. [PMID: 38481246 PMCID: PMC10935864 DOI: 10.1186/s13023-024-03084-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 02/13/2024] [Indexed: 03/17/2024] Open
Abstract
BACKGROUND Congenital generalized lipodystrophy (CGL) is a rare inherited disease characterized by a near-total absence of adipose tissue and is associated with organ system abnormalities and severe metabolic complications. Here, we have analyzed the disease characteristics of the largest CGL cohort from the Middle East and North Africa (MENA) who have not received lipodystrophy-specific treatment. METHODS CGL was diagnosed clinically by treating physicians through physical assessment and supported by genetic analysis, fat loss patterns, family history, and the presence of parental consanguinity. Data were obtained at the time of patient diagnosis and during leptin-replacement naïve follow-up visits as permitted by available medical records. RESULTS Data from 43 patients with CGL (37 females, 86%) were collected from centers located in eight countries. The mean (median, range) age at diagnosis was 5.1 (1.0, at birth-37) years. Genetic analysis of the overall cohort showed that CGL1 (n = 14, 33%) and CGL2 (n = 18, 42%) were the predominant CGL subtypes followed by CGL4 (n = 10, 23%); a genetic diagnosis was unavailable for one patient (2%). There was a high prevalence of parental consanguinity (93%) and family history (67%) of lipodystrophy, with 64% (n = 25/39) and 51% (n = 20/39) of patients presenting with acromegaloid features and acanthosis nigricans, respectively. Eighty-one percent (n = 35/43) of patients had at least one organ abnormality; the most frequently affected organs were the liver (70%, n = 30/43), the cardiovascular system (37%, n = 16/43) and the spleen (33%, n = 14/43). Thirteen out of 28 (46%) patients had HbA1c > 5.7% and 20/33 (61%) had triglyceride levels > 2.26 mmol/L (200 mg/dl). Generally, patients diagnosed in adolescence or later had a greater severity of metabolic disease versus those diagnosed during childhood; however, metabolic and organ system abnormalities were observed in a subset of patients diagnosed before or at 1 year of age. CONCLUSIONS This analysis suggests that in addition to the early onset of fat loss, family history and high consanguinity enable the identification of young patients with CGL in the MENA region. In patients with CGL who have not received lipodystrophy-specific treatment, severe metabolic disease and organ abnormalities can develop by late childhood and worsen with age.
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Affiliation(s)
| | - Afaf Alsagheir
- Pediatrics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Azza Al Shidhani
- Department of Child Health, Division of Endocrinology, Sultan Qaboos University Hospital, Al-Khod, Muscat, Oman
| | - Somaya Alzelaye
- Center of Endocrinology and Diabetes Mellitus, Al-Qunfudah General Hospital, Makkah Province, Al-Qunfudah, Saudi Arabia
| | - Nadia Alghazir
- Department of Pediatrics, Faculty of Medicine, Tripoli University Hospital, University of Tripoli, Tripoli, Libya
| | - Imad Brema
- Obesity, Endocrine, and Metabolism Center, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Hussain Alsaffar
- Department of Child Health, Division of Endocrinology, Sultan Qaboos University Hospital, Al-Khod, Muscat, Oman
| | - Mohammed Al Dubayee
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- Department of Medicine, Ministry of the National Guard-Health Affairs, Riyadh, Saudi Arabia
| | - Awad Alshahrani
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- Department of Medicine, Ministry of the National Guard-Health Affairs, Riyadh, Saudi Arabia
| | | | - Omneya M Omar
- Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Najya Attia
- King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
| | - Elham Al Amiri
- Al Qassimi Women & Children Hospital, Sharjah, United Arab Emirates
| | - Jamal Al Jubeh
- Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
| | | | - Haya Alkhayyat
- Bahrain Defence Force Royal Medical Services, Riffa, Bahrain
| | - Azad Haleem
- University of Duhok/College of Medicine, Duhok, Iraq
| | - Mouza Al Yahyaei
- National Diabetes and Endocrine Center, Royal Hospital, Muscat, Oman
| | - Ines Khochtali
- Internal Medicine and Endocrinology Department, Fattouma Bourguiba University Hospital, University of Monastir, Monastir, Tunisia, Monastir, Tunisia
| | - Saleha Babli
- Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Ahmed Nugud
- Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates
| | - Nandu Thalange
- Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates
- Department of Medicine, Mohammed Bin Rashid University, Dubai, United Arab Emirates
| | | | | | - Asma Deeb
- Pediatric Endocrine Division, Sheikh Shakhbout Medical City & College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates
| | - Majid Alfadhel
- Genetic and Precision Medicine Department, King Abdullah Specialized Children Hospital, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi Arabia
- College of Medicine, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNGH), Riyadh, Saudi Arabia
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16
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Shoaib AB. Islamic perspectives on preconception, prenatal, and perinatal counseling. Front Pediatr 2024; 12:1373918. [PMID: 38450297 PMCID: PMC10914958 DOI: 10.3389/fped.2024.1373918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Accepted: 02/08/2024] [Indexed: 03/08/2024] Open
Abstract
With advances in prenatal imaging, genetic testing, and medical treatment of premature neonates, new bioethical challenges have arisen. Many Muslims turn to their faith and religious leaders to help navigate these novel challenges. This article briefly discusses the factors that are involved in religious leaders issuing a fatwa, or religious opinion. Using clinical scenarios, this article reviews the current discourse amongst Islamic scholars and laws in Muslim-majority countries regarding challenging bioethical topics surrounding preconception counseling, antenatal testing and termination of pregnancy, as well as Islamic scholars' attempts to determine a minimum gestational age of viability using primary religious texts, the Quran and hadith. Challenges and shortcomings in the Islamic perspective on these issues are also addressed to highlight areas in which further research should be pursued. A deeper understanding of Islamic religious perspectives on these topics can help clinicians in providing care that is informed by patients' cultural and religious values.
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Affiliation(s)
- Abdullah Bin Shoaib
- Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, United States
- Division of Neurology, Children’s Medical Center, Dallas, TX, United States
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17
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Hajjaji M, Khadmaoui A, El Bakkali M. The practice of consanguineous marriage and the risk of diabetes among offspring in the province of Tetouan (Morocco). ARAB GULF JOURNAL OF SCIENTIFIC RESEARCH 2024; 42:30-43. [DOI: 10.1108/agjsr-08-2022-0134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
PurposeThe practice of consanguinity has been culturally preferred in most Arab countries, including Morocco. This behavior leads to an increase in genetic abnormalities, such as hypertension and diabetes. This paper examines the prevalence and determinants of first-cousin marriages and their impact on diabetes among offspring.Design/methodology/approachData on 882 couples were collected through face-to-face interview via a pre-established questionnaire based on the variables selected within the objectives of this study. The authors used the multiple logistic regression modeling procedure in this study.FindingsThe results of the study indicate that the prevalence of first-cousin marriages were 15% among students’ parents. From the multiple logistic regression modeling, the authors found a significant effect of paternal and maternal grandparents’ first-cousins marriage on that of parents (aOR = 3.27 and aOR = 3.36, respectively). However, an 11-fold higher risk of first relative marriages among parents once the paternal and maternal grandparents were first-cousins and the father was illiterate (aOR = 11.01). Moreover, the authors reported a diabetes risk of more than 14 times when the effects of first-cousin maternal grandparents and parents and the hypertension among mother or her sibling were combined (aOR = 14.48) or when the effects of first-cousins maternal grandparents, first-cousin parents and mother’s age at marriage between 21 and 29 years were combined (aOR = 14.56).Originality/valueFirst-cousin marriage depends on the father’s illiteracy and the consanguinity of grandparents’ factors. The cumulative effect of first-cousin marriage among grandparents, parents and a family history of hypertension among mother or her sibling increase the risk of diabetes among these mothers.
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18
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Alawad N, Alangari A, Allhybi A, Masud N, Almuzaini F, Alshamari M, Umair M, Alfadhel M. Assessment of attitudes towards the use of preimplantation genetic diagnosis in a single center in Riyadh, Saudi Arabia. J Genet Couns 2023; 32:1032-1039. [PMID: 37005789 DOI: 10.1002/jgc4.1713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 03/03/2023] [Accepted: 03/18/2023] [Indexed: 04/04/2023]
Abstract
In this cross-sectional study, we assessed the attitudes of the general public in Saudi Arabia regarding both medical and non-medical applications of pre-implantation genetic diagnosis (PGD). The study was conducted in King Abdullah Specialist Children's Hospital (KASCH) in Riyadh with a sample size of 377. Demographic information was collected, and attitudes towards applications of PGD were assessed using a pre-validated self-administered questionnaire. Out of the total sample size, 230 (61%) were males, 258 (68%) were married, 235 (63%) had one child or more, and 255 (68%) were older than 30 years of age representing the majority of participants. Only 87 (23%) of participants reported prior experience with PGD. Personally, knowing someone who had a prior experience with PGD was associated with higher attitude scores (more favorable attitudes towards PGD) (p-value = 0.04). The findings of this study indicate that our sample of Saudi individuals generally had a positive attitude towards the use of PGD.
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Affiliation(s)
- Nawaf Alawad
- King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
| | - Abdullah Alangari
- King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
| | - Abdulaziz Allhybi
- King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
| | - Nazish Masud
- King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
- Department of Medical Education, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Faisal Almuzaini
- King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
| | - Mohammed Alshamari
- King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
| | - Muhammad Umair
- Medical Genomic Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
| | - Majid Alfadhel
- King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
- Genetics and Precision Medicine department (GPM), King Abdullah Specialized Children's Hospital (KASCH), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia
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19
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Menor-Flores M, Vega-Rodríguez MA, Molina F. Iterative Level-0: A new and fast algorithm to traverse mating networks calculating the inbreeding and relationship coefficients. Comput Biol Med 2023; 164:107296. [PMID: 37566933 DOI: 10.1016/j.compbiomed.2023.107296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Revised: 06/24/2023] [Accepted: 07/28/2023] [Indexed: 08/13/2023]
Abstract
In population medical genetics, the study of autosomal recessive disorders in highly endogamous populations is a major topic where calculating the inbreeding and relationship coefficients on mating networks is crucial. However, a challenge arises when dealing with large and complex mating networks, making their traversal difficult during the calculation process. For this calculation, we propose using Iterative Level-0 (IL0) as a new and faster algorithm that traverses mating networks more efficiently. The purpose of this work is to explain in detail the IL0 algorithm and prove its superiority by comparing it with two algorithms based on the best-known algorithms in the area: Depth First Search (DFS) and Breadth First Search (BFS). A Cytoscape application has been developed to calculate the inbreeding and relationship coefficients of individuals composing any mating network. In this application, the IL0 proposal together with DFS-based and BFS-based algorithms have been implemented. Any user can access this freely available Cytoscape application (https://apps.cytoscape.org/apps/inbreeding) that allows the comparison between the IL0 proposal and the best-known algorithms (based on DFS and BFS). In addition, a diverse set of mating networks has been collected in terms of complexity (number of edges) and species (humans, primates, and dogs) for the experiments. The runtime obtained by the IL0, DFS-based, and BFS-based algorithms when calculating the inbreeding and relationship coefficients proved the improvement of IL0. In fact, a speedup study reflected that the IL0 algorithm is 7.60 to 127.50 times faster than DFS-based and BFS-based algorithms. Moreover, a scalability study found that the growth of the IL0 runtime has a linear dependence on the number of edges of the mating network, while the DFS-based and BFS-based runtimes have a quadratic dependence. Therefore, the IL0 algorithm can solve the problem of calculating the inbreeding and relationship coefficients many times faster (up to 127.50) than the two algorithms based on the famous DFS and BFS. Furthermore, our results demonstrate that IL0 scales much better as the complexity of mating networks increases.
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Affiliation(s)
- Manuel Menor-Flores
- Escuela Politécnica, Universidad de Extremadura(1), Campus Universitario s/n, 10003 Cáceres, Spain.
| | - Miguel A Vega-Rodríguez
- Escuela Politécnica, Universidad de Extremadura(1), Campus Universitario s/n, 10003 Cáceres, Spain.
| | - Felipe Molina
- Facultad de Ciencias, Universidad de Extremadura (1), Avda. de Elvas s/n, 06006 Badajoz, Spain.
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20
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Shaik NA, Al-Shehri N, Athar M, Awan A, Khalili M, Al Mahadi HB, Hejazy G, Saadah OI, Al-Harthi SE, Elango R, Banaganapalli B, Alefishat E, Awan Z. Protein structural insights into a rare PCSK9 gain-of-function variant (R496W) causing familial hypercholesterolemia in a Saudi family: whole exome sequencing and computational analysis. Front Physiol 2023; 14:1204018. [PMID: 37469559 PMCID: PMC10353052 DOI: 10.3389/fphys.2023.1204018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 06/12/2023] [Indexed: 07/21/2023] Open
Abstract
Familial hypercholesterolemia (FH) is a globally underdiagnosed genetic condition associated with premature cardiovascular death. The genetic etiology data on Arab FH patients is scarce. Therefore, this study aimed to identify the genetic basis of FH in a Saudi family using whole exome sequencing (WES) and multidimensional bioinformatic analysis. Our WES findings revealed a rare heterozygous gain-of-function variant (R496W) in the exon 9 of the PCSK9 gene as a causal factor for FH in this family. This variant was absent in healthy relatives of the proband and 200 healthy normolipidemic controls from Saudi Arabia. Furthermore, this variant has not been previously reported in various regional and global population genomic variant databases. Interestingly, this variant is classified as "likely pathogenic" (PP5) based on the variant interpretation guidelines of the American College of Medical Genetics (ACMG). Computational functional characterization suggested that this variant could destabilize the native PCSK9 protein and alter its secondary and tertiary structural features. In addition, this variant was predicted to negatively influence its ligand-binding ability with LDLR and Alirocumab antibody molecules. This rare PCSK9 (R496W) variant is likely to expand our understanding of the genetic basis of FH in Saudi Arabia. This study also provides computational structural insights into the genotype-protein phenotype relationship of PCSK9 pathogenic variants and contributes to the development of personalized medicine for FH patients in the future.
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Affiliation(s)
- Noor Ahmad Shaik
- Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- Princess Al-Jawhara Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Najla Al-Shehri
- Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mohammad Athar
- Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
- Science and Technology Unit, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Ahmed Awan
- Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mariam Khalili
- Department of Pharmacology, College of Medicine, Khalifa University, Abu Dhabi, United Arab Emirates
| | | | - Gehan Hejazy
- Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Omar I. Saadah
- Department of Pediatrics, Pediatric Gastroenterology Unit, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Sameer Eida Al-Harthi
- Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ramu Elango
- Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- Princess Al-Jawhara Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Babajan Banaganapalli
- Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- Princess Al-Jawhara Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Eman Alefishat
- Department of Pharmacology, College of Medicine, Khalifa University, Abu Dhabi, United Arab Emirates
- Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman, Jordan
- Center for Biotechnology, Khalifa University, Abu Dhabi, United Arab Emirates
| | - Zuhier Awan
- Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
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21
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Ford S, Ilgaz F, Hawker S, Cochrane B, Hill M, Ellerton C, MacDonald A. Amino Acid Analyses of Plant Foods Used in the Dietary Management of Inherited Amino Acid Disorders. Nutrients 2023; 15:nu15102387. [PMID: 37242270 DOI: 10.3390/nu15102387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 05/09/2023] [Accepted: 05/16/2023] [Indexed: 05/28/2023] Open
Abstract
A low amino acid (AA)/protein diet is the principal treatment for many inherited amino acid disorders (IMDs). Due to their low AA content, plant foods constitute an essential part of diet therapy. However, data on their AA composition are limited, which leads to an estimation of AA intake from protein content rather than an accurate calculation of true AA intake. This study describes the AA content of a total of 73 plant foods (fruits, n = 12; vegetables, n = 51; and other plant foods, n = 10), with the analysis commissioned by the UK National Society for Phenylketonuria (NSPKU) over 15 years. For all fruits and some vegetables (e.g., rocket, watercress and pea shoots), raw samples were used during analysis. All other vegetables were cooked prior to analysis to represent the usual condition of the food at the time of serving. AA analysis was performed with ion exchange chromatography. The median percentage of protein was 2.0% [0.6-5.4%] for the fruits and vegetables analysed (n = 56), although higher in vegetables than in fruits. Each of the five reported AAs (leucine, lysine, phenylalanine, tyrosine, and methionine) supplied 1-5% per g of protein content. From the heterogeneous range of plant foods analysed, the AA/protein ratios differed significantly (2-5% in fruits and 1-9% in vegetables). There was a strong correlation between the amounts of each of the five AAs in the plant foods, but only a small, moderate correlation between the protein and AA content. Overall, this study provides data on the AA content of several plant foods, which are suitable for patients treated with a low AA/protein diet, including many novel plant options. However, only a limited range of fruits and vegetables were analysed due to the high costs of analysis. Hence, more extensive studies with an increased number of plant foods prepared by different cooking methods and replicate samples are necessary, particularly to examine the relationship between the protein and AA content in depth.
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Affiliation(s)
- Suzanne Ford
- National Society for Phenylketonuria (NSPKU), Sheffield S12 9ET, UK
- Southmead Hospital North Bristol Trust, Bristol BS10 5NB, UK
| | - Fatma Ilgaz
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Hacettepe University, Ankara 06100, Turkey
| | | | - Barbara Cochrane
- NHS Greater Glasgow and Clyde, Royal Hospital for Children, Glasgow G51 4TF, UK
| | - Melanie Hill
- Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S5 7AU, UK
| | - Charlotte Ellerton
- University College London Hospitals NHS Foundation Trust, London WC1N 3BG, UK
| | - Anita MacDonald
- Birmingham Children's Hospital, Steelhouse Lane, Birmingham B4 6NH, UK
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22
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Tawfik SM, Elhosseiny AA, Galal AA, William MB, Qansuwa E, Elbaz RM, Salama M. Health inequity in genomic personalized medicine in underrepresented populations: a look at the current evidence. Funct Integr Genomics 2023; 23:54. [PMID: 36719510 DOI: 10.1007/s10142-023-00979-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 01/24/2023] [Accepted: 01/24/2023] [Indexed: 02/01/2023]
Abstract
Improvements in sequencing technology coupled with dramatic declines in the cost of genome sequencing have led to a proportional growth in the size and number of genetic datasets since the release of the human genetic sequence by The Human Genome Project (HGP) international consortium. The HGP was undeniably a significant scientific success, a turning point in human genetics and the beginning of human genomics. This burst of genetic information has led to a greater understanding of disease pathology and the potential of employing this data to deliver more precise patient care. Hence, the recognition of high-penetrance disease-causing mutations which encode drivers of disease has made the management of most diseases more specific. Nonetheless, while genetic scores are becoming more extensively used, their application in the real world is expected to be limited due to the lack of diversity in the data used to construct them. Underrepresented populations, such as racial and ethnic minorities, low-income individuals, and those living in rural areas, often experience greater health disparities and worse health outcomes compared to the general population. These disparities are often the result of systemic barriers, such as poverty, discrimination, and limited access to healthcare. Addressing health inequity in underrepresented populations requires addressing the underlying social determinants of health and implementing policies and programs which promoted health equity and reduce disparities. This can include expanding access to affordable healthcare, addressing poverty and unemployment, and promoting policies that combat discrimination and racism.
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Affiliation(s)
- Sherouk M Tawfik
- Institute of Global Health and Human Ecology, School of Sciences and Engineering, The American University in Cairo, Cairo, 11835, Egypt.,Department of Pharmacology and Biochemistry, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo, 11837, Egypt
| | - Aliaa A Elhosseiny
- Institute of Global Health and Human Ecology, School of Sciences and Engineering, The American University in Cairo, Cairo, 11835, Egypt.,Department of Pharmacology and Biochemistry, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo, 11837, Egypt
| | - Aya A Galal
- Institute of Global Health and Human Ecology, School of Sciences and Engineering, The American University in Cairo, Cairo, 11835, Egypt.,Systems Genomics Laboratory, The American University in Cairo, New Cairo, Egypt
| | - Martina B William
- Institute of Global Health and Human Ecology, School of Sciences and Engineering, The American University in Cairo, Cairo, 11835, Egypt.,Department of Clinical Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt
| | - Esraa Qansuwa
- Institute of Global Health and Human Ecology, School of Sciences and Engineering, The American University in Cairo, Cairo, 11835, Egypt
| | - Rana M Elbaz
- Institute of Global Health and Human Ecology, School of Sciences and Engineering, The American University in Cairo, Cairo, 11835, Egypt
| | - Mohamed Salama
- Institute of Global Health and Human Ecology, School of Sciences and Engineering, The American University in Cairo, Cairo, 11835, Egypt. .,Faculty of Medicine, Mansoura University, Mansoura, Egypt. .,Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland.
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23
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Afifi HH, Gaber KR, Thomas MM, Taher MB, Tosson AMS. Genetic Implications in High-Risk Pregnancy and Its Outcome: A 2-Year Study. Am J Perinatol 2022; 39:1659-1667. [PMID: 33636738 DOI: 10.1055/s-0041-1724002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
OBJECTIVE The aim of this study is to evaluate high-risk pregnant females' offspring as regard the presence of any medical condition, hereditary disorder, or major anomaly as well as to document parental sociodemographic characteristics and compliance with follow-up schedules of fetal medicine and clinical genetic clinics. STUDY DESIGN This prospective 2-year cohort study of neonates and infants reported the referral indications, investigations, and diagnoses obtained through prenatal and postnatal examinations. It also reported their parental follow-up vigilance. RESULTS Of the 811 infants of high risk females referred 460 (56.7%) came for assessment. Mean parental consanguinity and endogamy were 67 and 71.3%, respectively. All pregnant mothers underwent first-trimester biochemical testing (plasma protein-A, α-fetoprotein [AFP], human chorionic gonadotropin [hCG]) and serial ultrasound examinations. Seventy mothers needed second-trimester biochemical testing (AFP, hCG, and estriol). Sixty-two mothers underwent amniocentesis where G-banding karyotype, fluorescence in situ hybridization and targeted molecular testing for the specific gene mutation of single gene disorders were conducted according to suspected disorders. High quality fetal ultrasound was performed when brain malformations were suspected, while 16 fetuses required brain MRI examination. Mean age of newborns at first examination was 26.5 days. They were grouped according to the maternal indication for referral. Upon examination, 18 neonates had confirmed congenital malformations/genetic disorders. Five of them were diagnosed prenatally. In four other fetuses with single gene disorder, the molecular diagnosis of their affected siblings was not established prior to this pregnancy; thus, prenatal diagnosis was not possible. The remaining nine cases were diagnosed postnatally. CONCLUSION Parental consanguinity and endogamy were increased among high-risk pregnancies. Public awareness about potential adverse effects of consanguineous marriages and the importance of genetic testing are imperative. A structured multidisciplinary team of specialists in fetal medicine, clinical genetics, and neonatology provides good genetic services. Expansion and financial support of these services are urgently required. KEY POINTS · A multidisciplinary team provides good genetic services in high-risk pregnancies.. · Parental consanguinity and endogamy are increased among high-risk pregnancies.. · Increased public awareness about genetic testing importance and financial support are imperative..
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Affiliation(s)
- Hanan H Afifi
- Division of Human Genetics and Genome Research, Department of Clinical Genetics, Developmental Assessment and Genetic Disorders Clinic, National Research Centre, Cairo, Egypt
| | - Khaled R Gaber
- Division of Human Genetics and Genome Research, Department of Prenatal Diagnosis and Fetal Medicine, National Research Centre, Cairo, Egypt
| | - Manal M Thomas
- Division of Human Genetics and Genome Research, Department of Clinical Genetics, Developmental Assessment and Genetic Disorders Clinic, National Research Centre, Cairo, Egypt
| | - Mohamed B Taher
- Division of Human Genetics and Genome Research, Department of Clinical Genetics, Developmental Assessment and Genetic Disorders Clinic, National Research Centre, Cairo, Egypt
| | - Angie M S Tosson
- Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt
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24
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Consanguinity in the Chaouia population (Morocco): prevalence, trends, determinants, fertility, and spontaneous abortions. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2022. [DOI: 10.1186/s43042-022-00337-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
One of the aspects that helps to understand the genetic structure of a population throughout its biological history is the description of its matrimonial practices. Thus, the objective of this study is to explore consanguinity, one of these practices, to its full extent by identifying the prevalence, determinants, and trends of a consanguineous marriage, as well as its impact on fertility and spontaneous abortions in the Chaouia population, a region located in the western center of Morocco. Therefore, a survey-based cross-sectional study was conducted between January 2019 and January 2020. The sample was collected by province using a stratified random sampling approach, yielding a sample of 788 people. The association between consanguinity and socioeconomic and demographic characteristics, as well as reproductive health and pregnancy outcomes, was described using chi-square and ANOVA analysis. Multivariate logistic regression analysis was used to determine the predictors of a consanguineous marriage.
Results
Our findings revealed a consanguinity rate of 25.38%. The mean inbreeding coefficient was 0.012214. The most common type of union was between first cousins. This practice was strongly associated with an early age at marriage for both genders and with endogamy and immobility of couples, according to their place of birth. Consanguinity was significantly associated with fertility (p < 0.001) and spontaneous abortions (p = 0.029). The average number of pregnancies and spontaneous abortions was higher in consanguineous unions (5.18 ± 0.20/0.47 ± 0.08) compared to non-consanguineous unions (4.33 ± 0.10/0.31 ± 0.03).
Conclusions
Consanguinity is a deeply rooted social and cultural tradition in this population, providing individuals with a sense of social-economic stability while assuring their attachment to the group. Despite being highly associated with fertility, this practice has a significant influence on pregnancy outcomes, namely spontaneous abortions. Therefore, further studies are needed to examine the impact of consanguinity on various aspects of reproductive health and its association with numerous genetic abnormalities and diseases.
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25
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Abd El-Kader RG, Saleh LM. University Students Attitude Towards the National Premarital Screening Program of UAE. EUROPEAN JOURNAL OF ENVIRONMENT AND PUBLIC HEALTH 2022; 6:em0109. [DOI: 10.21601/ejeph/12022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
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26
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Zaien SZ, El-Houfey AA, Alqahtani H, El Sayed HAE, Elgzar WT, Essa RM, Bayomy H, Ibrahim HAF. Predictors of premarital screening and genetic counseling knowledge and attitude among deaf and hard hearing females in Tabuk, Saudi Arabia. J Med Life 2022; 15:379-386. [PMID: 35450002 PMCID: PMC9015174 DOI: 10.25122/jml-2021-0165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 12/27/2021] [Indexed: 11/21/2022] Open
Abstract
According to Saudi Arabia's 2030 vision, research should be directed to prevention, early detection, and intervention to reduce all types of disability. The current study aimed to investigate the predictors of Premarital Screening and Genetic Counseling (PMSGC) knowledge and attitude among deaf and hard hearing females' in Tabuk, Saudi Arabia. Descriptive correlational design was conducted on a convenience sample of 67 deaf and hard hearing students from the Tabuk region. Data were collected by an electronic questionnaire elaborated to the participants using sign language. The results revealed that most participants had incorrect answers regarding most PMSGC questions. Around two-thirds (68.7%, 65.7%, and 71.6%) of them strongly agree that PMSGC is very important, compatible with Islamic principles, and prevents family social and psychological problems, respectively. Older, urban area residents and university-educated participants have significantly higher knowledge and attitude scores than their peers (t=2.239, 4.887, 4.790 & p<0.05), respectively. Multiple regression shows that age (b=0.302, t=-2.795, p=0.007), education (b=0.336, t=2.425, p=0.019), mothers' education (b=0.314, t=2.345, p=0.023), and monthly income (b=-0.337, t=-2.503, p=0.015), are significant predictors of PMSGC knowledge. Furthermore, age (b=0.659, t=4.024, p=0.000), residence (b=0.293, t=2.233, p=0.030), education (b=-0.395, t=3.028, p=0.004), and type of disability (b=-0.443, t=-3.763, p=0.000) are significant predictors of PMSGC attitude. Although most deaf and hard hearing females have incorrect knowledge regarding PMSGC, most have a positive attitude. The study concluded that participants' education, mothers' education, and monthly income are significant predictors of PMSGC knowledge. Moreover, age, residence, education, and type of disability were significant predictors of higher PMSGC attitudes.
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Affiliation(s)
- Sahar Zedan Zaien
- Department of Special Education, College of Art & Education, Tabuk University, Tabuk, Saudi Arabia
| | - Amira Abdallah El-Houfey
- Community Health Nursing, Faculty of Nursing, Assiut University, Assiut, Egypt,Department of Nursing, Jizan University, Jizan, Saudi Arabia
| | - Hanadi Alqahtani
- Department of Special Education, College of Art & Education, Tabuk University, Tabuk, Saudi Arabia
| | - Hanan Abd Elwahab El Sayed
- Department of Medical Science Assistance, Community College, Tabuk University, Tabuk, Saudi Arabia,Department of Community Health Nursing, Faculty of Nursing, Benha University, Benha, Egypt
| | - Wafaa Taha Elgzar
- Department of Obstetrics and Gynecologic Nursing, Damanhour University, Damanhour, Egypt,Department of Maternity and Childhood Nursing, Nursing College, Najran University, Najran, Saudi Arabia,Corresponding Author: Wafaa Taha Elgzar, Department of Maternity and Childhood Nursing, Nursing college, Najran University, Najran, Saudi Arabia. E-mail: ;
| | - Rasha Mohamed Essa
- Department of Obstetrics and Gynecologic Nursing, Damanhour University, Damanhour, Egypt
| | - Hala Bayomy
- Department of Nutrition and Food Science, University of Tabuk, Tabuk, Saudi Arabia,Department of Food Science and Technology, Damanhour University, Damanhour, Egypt
| | - Heba Abdel-Fatah Ibrahim
- Department of Maternity and Childhood Nursing, Nursing College, Najran University, Najran, Saudi Arabia,Department of Obstetrics and Woman Health Nursing, Benha University, Benha, Egypt
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27
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Susgun S, Kasan K, Yucesan E. Gene Hunting Approaches through the Combination of Linkage Analysis with Whole-Exome Sequencing in Mendelian Diseases: From Darwin to the Present Day. Public Health Genomics 2022; 24:207-217. [PMID: 34237751 DOI: 10.1159/000517102] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 04/27/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND In the context of medical genetics, gene hunting is the process of identifying and functionally characterizing genes or genetic variations that contribute to disease phenotypes. In this review, we would like to summarize gene hunting process in terms of historical aspects from Darwin to now. For this purpose, different approaches and recent developments will be detailed. SUMMARY Linkage analysis and association studies are the most common methods in use for explaining the genetic background of hereditary diseases and disorders. Although linkage analysis is a relatively old approach, it is still a powerful method to detect disease-causing rare variants using family-based data, particularly for consanguineous marriages. As is known that, consanguineous marriages or endogamy poses a social problem in developing countries, however, this same condition also provides a unique opportunity for scientists to identify and characterize pathogenic variants. The rapid advancements in sequencing technologies and their parallel implementation together with linkage analyses now allow us to identify the candidate variants related to diseases in a relatively short time. Furthermore, we can now go one step further and functionally characterize the causative variant through in vitro and in vivo studies and unveil the variant-phenotype relationships on a molecular level more robustly. Key Messages: Herein, we suggest that the combined analysis of linkage and exome analysis is a powerful and precise tool to diagnose clinically rare and recessively inherited conditions.
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Affiliation(s)
- Seda Susgun
- Department of Medical Biology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey.,Graduate School of Health Sciences, Istanbul University, Istanbul, Turkey
| | - Koray Kasan
- Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
| | - Emrah Yucesan
- Department of Medical Biology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
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Alkalbani A, Alharrasi M, Achura S, Al Badi A, Al Rumhi A, Alqassabi K, Almamari R, Alomari O. Factors Affecting the Willingness to Undertake Premarital Screening Test Among Prospective Marital Individuals. SAGE Open Nurs 2022; 8:23779608221078156. [PMID: 35237718 PMCID: PMC8882947 DOI: 10.1177/23779608221078156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 01/17/2022] [Indexed: 11/21/2022] Open
Abstract
Introduction Awareness toward premarital screening test and its influence on preventing
high risk marriages has become a concern to the health care system in Oman.
This is due to the increased rates of inherited diseases and genetic
disorders among the Omani population secondary to consanguineous
marriages. Objectives This cross-sectional study aims to describe the utilization of premarital
screening tests of selected university study participants as future
prospective couples. Methods The study included 400 Omani study participants from different majors at a
national governmental university that receives students from all over the
country. Data was collected using a self-administered questionnaire. Results Out of the 400 study participants 193 [48.3%] were females and 195 [48.8%]
were males, and 380 [95%] were unmarried and 19 [4.8%] were married.
Personal and family history of hereditary diseases and consanguinity between
parents were reported by 40 participants [10%], 158 [39.5%] and 175 [43.8%]
respectively. Three hundred and sixty-one [90.3%] of the total participants
were aware of the availability of premarital screening tests in Oman. A
total of 357 [89.3%] thought it is necessary to do a premarital screening
test and 367 [91.8%] agreed to carry out it in the future. The novel
contribution of this manuscript is that our logistic regression showed that
people with personal or family history of hereditary disease, and have
consanguinity between parents, being a female did not show willingness to
undertake the screening while those who are married, have higher GPA, and
older supported it. Conclusion Usability of the freely available premarital screening is low despite the
study participants awareness and willingness. Future studies should target
those who have a history of genetic disease and females as we found them not
willing to undertake the test in this study. We also recommend putting in
place mandatory rules and regulations for premarital screening tests with
better counselling strategies.
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Affiliation(s)
| | | | - Susan Achura
- Sultan Qaboos University, College of Nursing, Muscat, Oman
| | | | | | | | - Raya Almamari
- Sultan Qaboos University, College of Nursing, Muscat, Oman
| | - Omar Alomari
- Sultan Qaboos University, College of Nursing, Muscat, Oman
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Campbell OLK, Mace R. Different predictors of intimate partner and natal family violence against women. Evol Med Public Health 2022; 10:231-242. [PMID: 35663510 PMCID: PMC9154062 DOI: 10.1093/emph/eoac019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 04/06/2022] [Indexed: 11/25/2022] Open
Abstract
Background Violence against women is often studied in the context of violence from intimate partners. However, women receive violence from a wider range of individuals—such as their natal kin—including their siblings, parents, uncles and cousins. Applying insights from evolutionary theory, we examine whether cousin marriage, which has been hypothesized to both reduce the risk of partner violence but increase the risk of natal family violence, associates differently with each type of violence. Second, we test whether common risk factors for partner violence, such as wealth, associate similarly with natal violence. Methodology We analyse over 16 000 Jordanian women from three cohorts of the Jordan Demographic Health Surveys. Predictor variables include type of cousin marriage (patrilateral or matrilateral), education, wealth, number of children, urban living and polygyny. Outcome variables include whether a woman’s husband or her natal family has ever been physically violent towards her. Results Being married to a patrilateral cousin but not a matrilateral cousin is associated with a reduced risk of reporting intimate partner violence (IPV). By contrast being married to a matrilateral cousin but not a patrilateral one is associated with a reduced risk of reporting natal family violence. As expected, wealth is negatively associated with reporting partner violence, but we find no association with reports of natal family violence. Finally, individuals with more children are more likely to report IPV. Conclusions and implications Findings indicate the importance of distinguishing between types of cousin marriage and highlight substantial differences in risk factors for intimate partner compared to natal family violence. Lay Summary Sociodemographic risk factors, such as wealth, may associate differently with intimate partner and natal family violence. Results suggest that whether cousin marriage is protective of violence may depend on the type of cousin and secondly, that violence can have fitness relevant outcomes.
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Affiliation(s)
| | - Ruth Mace
- Department of Anthropology, University College London , London WC1H 0BW, UK
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Rafique I, Mir A, Saqib MAN, Naeem M, Marchand L, Polychronakos C. Causal variants in Maturity Onset Diabetes of the Young (MODY) - A systematic review. BMC Endocr Disord 2021; 21:223. [PMID: 34763692 PMCID: PMC8582101 DOI: 10.1186/s12902-021-00891-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 10/28/2021] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Maturity Onset Diabetes of the Young (MODY) is an autosomal dominant type of diabetes. Pathogenic variants in fourteen genes are reported as causes of MODY. Its symptoms overlap with type 1 and type 2 diabetes. Reviews for clinical characteristics, diagnosis and treatments are available but a comprehensive list of genetic variants, is lacking. Therefore this study was designed to collect all the causal variants involved in MODY, reported to date. METHODS We searched PubMed from its date of inception to December 2019. The search terms we used included disease names and name of all the known genes involved. The ClinVar database was also searched for causal variants in the known 14 MODY genes. RESULTS The record revealed 1647 studies and among them, 326 studies were accessed for full-text. Finally, 239 studies were included, as per our inclusion criteria. A total of 1017 variants were identified through literature review and 74 unpublished variants from Clinvar database. The gene most commonly affected was GCK, followed by HNF1a. The traditional Sanger sequencing was used in 76 % of the cases and 65 % of the studies were conducted in last 10 years. Variants from countries like Jordan, Oman and Tunisia reported that the MODY types prevalent worldwide were not common in their countries. CONCLUSIONS We expect that this paper will help clinicians interpret MODY genetics results with greater confidence. Discrepancies in certain middle-eastern countries need to be investigated as other genes or factors, like consanguinity may be involved in developing diabetes.
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Affiliation(s)
- Ibrar Rafique
- Department of Biological Sciences, International Islamic University, Islamabad, Pakistan
- Graduate Research Trainee, Department of Pediatrics and Human Genetics, McGill University Health Centre Research Institute, Montreal, Canada
- Research Officer, Pakistan Health Research Council, Sector G-5/2, Islamabad, Pakistan
| | - Asif Mir
- Department of Biological Sciences, International Islamic University, Islamabad, Pakistan.
| | | | - Muhammad Naeem
- Department of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan
| | - Luc Marchand
- Department of Pediatrics and Human Genetics, McGill University Health Centre Research Institute, Montreal, Canada
| | - Constantin Polychronakos
- Departments of Pediatrics and Human Genetics, McGill University Health Centre Research Institute, 1001 Decarie Boulevard, Montréal, Québec, Canada.
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31
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El-Kebbi IM, Bidikian NH, Hneiny L, Nasrallah MP. Epidemiology of type 2 diabetes in the Middle East and North Africa: Challenges and call for action. World J Diabetes 2021; 12:1401-1425. [PMID: 34630897 PMCID: PMC8472500 DOI: 10.4239/wjd.v12.i9.1401] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 06/21/2021] [Accepted: 08/02/2021] [Indexed: 02/06/2023] Open
Abstract
Type 2 diabetes continues to be a serious and highly prevalent public health problem worldwide. In 2019, the highest prevalence of diabetes in the world at 12.2%, with its associated morbidity and mortality, was found in the Middle East and North Africa region. In addition to a genetic predisposition in its population, evidence suggests that obesity, physical inactivity, urbanization, and poor nutritional habits have contributed to the high prevalence of diabetes and prediabetes in the region. These risk factors have also led to an earlier onset of type 2 diabetes among children and adolescents, negatively affecting the productive years of the youth and their quality of life. Furthermore, efforts to control the rising prevalence of diabetes and its complications have been challenged and complicated by the political instability and armed conflict in some countries of the region and the recent coronavirus disease 2019. Broad strategies, coupled with targeted interventions at the regional, national, and community levels are needed to address and curb the spread of this public health crisis.
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Affiliation(s)
- Imad M El-Kebbi
- Department of Internal Medicine, Division of Endocrinology, American University of Beirut Medical Center, Faculty of Medicine, Beirut 11072020, Lebanon
- Department of Internal Medicine, Sheikh Shakhbout Medical City, Abou Dhabi 11001, United Arab Emirates
| | - Nayda H Bidikian
- School of Medicine, American University of Beirut, Faculty of Medicine, Beirut 11072020, Lebanon
| | - Layal Hneiny
- University Libraries, Saab Medical Library, American University of Beirut, Beirut 11072020, Lebanon
| | - Mona Philippe Nasrallah
- Department of Internal Medicine, Division of Endocrinology, American University of Beirut Medical Center, Faculty of Medicine, Beirut 11072020, Lebanon
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Abolhassani H, Azizi G, Sharifi L, Yazdani R, Mohsenzadegan M, Delavari S, Sohani M, Shirmast P, Chavoshzadeh Z, Mahdaviani SA, Kalantari A, Tavakol M, Jabbari-Azad F, Ahanchian H, Momen T, Sherkat R, Sadeghi-Shabestari M, Aleyasin S, Esmaeilzadeh H, Al-Herz W, Bousfiha AA, Condino-Neto A, Seppänen M, Sullivan KE, Hammarström L, Modell V, Modell F, Quinn J, Orange JS, Aghamohammadi A. Global systematic review of primary immunodeficiency registries. Expert Rev Clin Immunol 2021; 16:717-732. [PMID: 32720819 DOI: 10.1080/1744666x.2020.1801422] [Citation(s) in RCA: 80] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION During the last 4 decades, registration of patients with primary immunodeficiencies (PID) has played an essential role in different aspects of these diseases worldwide including epidemiological indexes, policymaking, quality controls of care/life, facilitation of genetic studies and clinical trials as well as improving our understanding about the natural history of the disease and the immune system function. However, due to the limitation of sustainable resources supporting these registries, inconsistency in diagnostic criteria and lack of molecular diagnosis as well as difficulties in the documentation and designing any universal platform, the global perspective of these diseases remains unclear. AREAS COVERED Published and unpublished studies from January 1981 to June 2020 were systematically reviewed on PubMed, Web of Science and Scopus. Additionally, the reference list of all studies was hand-searched for additional studies. This effort identified a total of 104614 registered patients and suggests identification of at least 10590 additional PID patients, mainly from countries located in Asia and Africa. Molecular defects in genes known to cause PID were identified and reported in 13852 (13.2% of all registered) patients. EXPERT OPINION Although these data suggest some progress in the identification and documentation of PID patients worldwide, achieving the basic requirement for the global PID burden estimation and registration of undiagnosed patients will require more reinforcement of the progress, involving both improved diagnostic facilities and neonatal screening.
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Affiliation(s)
- Hassan Abolhassani
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences , Tehran, Iran.,Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge , Stockholm, Sweden
| | - Gholamreza Azizi
- Non-Communicable Diseases Research Center, Alborz University of Medical Sciences , Karaj, Iran
| | - Laleh Sharifi
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences , Tehran, Iran.,Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Yazdani
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences , Tehran, Iran
| | - Monireh Mohsenzadegan
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences , Tehran, Iran
| | - Samaneh Delavari
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences , Tehran, Iran.,Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences Iran University of Medical Sciences, Tehran, Iran
| | - Mahsa Sohani
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences , Tehran, Iran
| | - Paniz Shirmast
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences , Tehran, Iran
| | - Zahra Chavoshzadeh
- Pediatric Infections Research Center, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences , Tehran, Iran
| | - Seyed Alireza Mahdaviani
- Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases(NRITLD), Shahid Beheshti University of Medical Sciences , Tehran, Iran
| | - Arash Kalantari
- Department of Immunology and Allergy, Imam Khomeini Hospital, Tehran University of Medical Sciences , Tehran, Iran
| | - Marzieh Tavakol
- Non-Communicable Diseases Research Center, Alborz University of Medical Sciences , Karaj, Iran
| | | | - Hamid Ahanchian
- Allergy Research Center, Mashhad University of Medical Sciences , Mashhad, Iran
| | - Tooba Momen
- Department of Allergy and Clinical Immunology, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences , Isfahan, Iran
| | - Roya Sherkat
- Acquired Immunodeficiency Research Center, Lsfahan University of Medical Sciences , Isfahan, Lran
| | - Mahnaz Sadeghi-Shabestari
- Immunology research center of Tabriz, TB and lung research center of Tabriz, Children Hospital, Tabriz University of Medical Science , Tabriz, Iran
| | - Soheila Aleyasin
- Allergy Research Center, Shiraz University of Medical Sciences , Shiraz, Iran
| | | | - Waleed Al-Herz
- Department of Pediatrics, Kuwait University , Kuwait City, Kuwait.,Allergy and Clinical Immunology Unit, Department of Pediatrics, Al-Sabah Hospital , Kuwait City, Kuwait
| | - Ahmed Aziz Bousfiha
- Laboratoire d'Immunologie Clinique, d'Inflammation Et d'Allergie LICIA, Faculty of Medicine and Pharmacy, Hassan II University , Casablanca, Morocco.,Clinical Immunology Unit, Casablanca Children's Hospital, Ibn Rochd Medical School, Hassan II University , Casablanca, Morocco.,The African Society for Immunodeficiencies (ASID) Registry
| | - Antonio Condino-Neto
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo , São Paulo, Brazil.,The Latin American Society for Immunodeficiencies (LASID) Registry
| | - Mikko Seppänen
- Adult Immunodeficiency Unit, Infectious Diseases, Inflammation Center, University of Helsinki and Helsinki University Hospital , Helsinki, Finland.,Rare Disease Center and Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital , Helsinki, Finland.,European Society for Immunodeficiencies (ESID) Registry
| | - Kathleen E Sullivan
- Division of Allergy Immunology, Department of Pediatrics, The Children's Hospital of Philadelphia , Philadelphia, PA, USA.,The United States Immunodeficiency Network (USIDNET) Registry
| | - Lennart Hammarström
- Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge , Stockholm, Sweden
| | - Vicki Modell
- Jeffrey Modell Foundation (JMF) , New York City, NY, USA
| | - Fred Modell
- Jeffrey Modell Foundation (JMF) , New York City, NY, USA
| | - Jessica Quinn
- Jeffrey Modell Foundation (JMF) , New York City, NY, USA
| | - Jordan S Orange
- Jeffrey Modell Foundation (JMF) , New York City, NY, USA.,Department of Pediatrics, Columbia University College of Physicians and Surgeons , New York, NY, USA
| | - Asghar Aghamohammadi
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences , Tehran, Iran.,Iranian Primary Immunodeficiencies Network (IPIN), Tehran University of Medical Science , Tehran, Iran.,Asia Pacific Society for Immunodeficiencies (APSID) Registry
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Abstract
Introduction: Rare bleeding disorders (RBDs) are a heterogeneous group of bleeding disorders. Consanguineous marriage is the favorite partnership in many communities among a population of more than a billion. Consanguineous marriages allow the defective recessive genes in RBDs to remain in the family. Clinical approach to RBDs is not as straightforward as typical bleeding disorders, which are secondary to scarcity and variation of RBDs. However, in many developing countries, the limitations of diagnostic facilities, the supply of therapeutic coagulation concentrates, health budgets, and optimal health-care infrastructures may intensify the clinical practice of RBDs.Areas covered: The author addresses the role of consanguineous marriage in the incidence of RBDs and what preventive steps can be considered to minimize the incidence of RBDs. A literature review of PubMed and google Scholar was conducted in November of 2020 using the relevant keywords.Expert opinion: This review addresses the prevalence of consanguineous marriages in Middle Eastern countries and the various reasons behind the coexistence of consanguineous marriage with RBDs. Finally, prevention steps that may be considered by health-care systems to minimize the incidence of rare bleeding disorders have been discussed. Health-care systems should train partners with the intention of consanguineous marriage on the downside of consanguinity.
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Affiliation(s)
- Hassan Mansouritorghabeh
- Central Diagnostic Laboratories, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
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From the President of the International Atherosclerosis Society: The Iraqi Lipid Clinics Network. J Clin Lipidol 2021; 15:538-539. [PMID: 34215562 DOI: 10.1016/j.jacl.2021.04.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 04/22/2021] [Indexed: 11/21/2022]
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Halim NA, Sayed RE, Alameh IA, Khoury J, Nakib CE, Zerdan MB, Charafeddine M, Farhat F, Karak FE, Assi HI. Safety and efficacy of pazopanib as a second-line treatment and beyond for soft tissue sarcomas: A real-life tertiary-center experience in the MENA region. Cancer Treat Res Commun 2020; 26:100275. [PMID: 33340905 DOI: 10.1016/j.ctarc.2020.100275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 11/27/2020] [Accepted: 12/09/2020] [Indexed: 11/16/2022]
Abstract
INTRODUCTION Sarcomas are uncommon malignancies. No advances have been recently achieved despite multiple efforts. Pazopanib is a safe and effective tyrosine kinase inhibitor used in managing soft tissue sarcomas (STS) after chemotherapy failure. However, its use is limited in developing countries and no efficacy data exist from our region. We aimed to study the efficacy of pazopanib in our population, characterized by response rates of patients with chemotherapy-refractory advanced STS receiving pazopanib. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and toxicity profile. MATERIALS AND METHODS 15 patients (age≥18 year) diagnosed with advanced STS, refractory to first-line chemotherapy, receiving pazopanib as ≥second-line therapy in one tertiary center in Lebanon were included between January 1st, 2014 and October 31st, 2018. Patient and disease characteristics, disease evaluation, as well as tolerance to treatment, were extracted from charts retrospectively. Statistical analysis was done using SPSS version 24. RESULTS The mean age was 48.6 [19-66] years. Eleven patients (73.3%) received pazopanib in second-line, whereas four patients (26.7%) received it in third-line. Thirteen patients (86.7%) progressed, and two patients (13.3%) had stable disease. The median PFS was three months [1-19] and the mean OS was 25.4 months [17.2-33.6]. Five patients required dose-reductions due to poor tolerance. CONCLUSION Conclusions cannot be drawn due to small patient numbers. However, given the 3-month PFS, 13% of patients maintaining stable disease, and tolerable safety profile, it is reasonable to incorporate pazopanib in STS treatment. More focused studies with larger patient populations need to be done in Lebanon.
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Affiliation(s)
- Nour Abdul Halim
- Department of Internal Medicine, Division of Hematology and Oncology, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Rola El Sayed
- Department of Internal Medicine, Division of Hematology and Oncology, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Ibrahim A Alameh
- Department of Internal Medicine, Division of Hematology and Oncology, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Jessica Khoury
- Department of Internal Medicine, Division of Hematology and Oncology, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Clara El Nakib
- Department of Internal Medicine, Division of Hematology and Oncology, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Maroun Bou Zerdan
- Department of Internal Medicine, Division of Hematology and Oncology, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Maya Charafeddine
- Department of Internal Medicine, Division of Hematology and Oncology, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Fadi Farhat
- Department of Internal Medicine, Division of Hematology and Oncology, Hammoud Hospital University Medical Center, Saida, Lebanon
| | - Fadi El Karak
- Department of Internal Medicine, Division of Hematology and Oncology, Hotel Dieu de France University Hospital, Beirut, Lebanon
| | - Hazem I Assi
- Department of Internal Medicine, Division of Hematology and Oncology, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon.
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Genetic and reproductive consequences of consanguineous marriage in Bangladesh. PLoS One 2020; 15:e0241610. [PMID: 33253173 PMCID: PMC7703949 DOI: 10.1371/journal.pone.0241610] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 09/15/2020] [Indexed: 12/22/2022] Open
Abstract
Introduction This study aimed to assess the prevalence, sociodemographic factors, reproductive consequences, and heritable disease burdens associated with consanguineous marriage (CM) in Bangladesh. Methods A total of 7,312 families, including 3,694 CM-families, were recruited from 102 locales of 58 districts of Bangladesh. Using a standard questionnaire, we collected medical history and background sociodemographic data of these families. Family history was assessed by pedigree analysis. Fertility, mortality, secondary sex ratio, selection intensity, lethal equivalents were measured using standard methods. Results The mean prevalence of CM in our studied population was 6.64%. Gross fertility was higher among CM families, as compared to the non-CM families (p < 0.05). The rate of under-5 child (U5) mortality was significantly higher among CM families (16.6%) in comparison with the non-CM families (5.8%) (p < 0.01). We observed a persuasive rise of abortion/miscarriage and U5 mortality rates with the increasing level of inbreeding. The value of lethal equivalents per gamete found elevated for autosomal inheritances as compared to sex-linked inheritance. CM was associated with the incidence of several single-gene and multifactorial diseases, and congenital malformations, including bronchial asthma, hearing defect, heart diseases, sickle cell anemia (p < 0.05). The general attitude and perception toward CM were rather indifferent, and very few people were concerned about its genetic burden. Conclusion This study highlights the harmful consequences of CM on reproductive behavior and the incidence of hereditary conditions. It essences the need for genetic counseling from premarital to postnatal levels in Bangladesh.
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Yaylacioglu Tuncay F, Guntekin Ergun S, Oner A, Turan A, Ozmert E, Ergun MA, Ozdek S. Inherited eye diseases in Turkey: Current approaches and future directions. AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS 2020; 184:773-781. [PMID: 32864844 DOI: 10.1002/ajmg.c.31829] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 07/27/2020] [Accepted: 07/28/2020] [Indexed: 01/01/2023]
Abstract
The aim of this review is to reveal Turkey's current status of medical practice in inherited eye diseases and the necessary steps to improve healthcare services and research activities in this area. Since consanguinity rate is high, disease burden is estimated to be high in Turkey. Universal health insurance system, easily accessible medical specialists, increasing genetic test, and counseling opportunities are the key advantages of Turkey's healthcare system. However, specialized clinics for inherited eye diseases, low-vision rehabilitation services, training of ophthalmologists about the recent developments in ocular genetics, and multidisciplinary translational research are the main headlines needed to be focused for better health services and successful research in Turkey.
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Affiliation(s)
| | - Sezen Guntekin Ergun
- Department of Medical Biology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Ayse Oner
- Ophthalmology Clinic, Acıbadem Atakent Kayseri Hospital, Kayseri, Turkey
| | - Ayse Turan
- Department of Ophthalmology, Yıldırım Beyazıt Faculty of Medicine, Ankara, Turkey
| | - Emin Ozmert
- Department of Ophthalmology, Ankara University Faculty of Medicine, Ankara, Turkey
| | - Mehmet Ali Ergun
- Department of Medical Genetics, Gazi University Faculty of Medicine, Ankara, Turkey
| | - Sengul Ozdek
- Department of Ophthalmology, Gazi University Faculty of Medicine, Ankara, Turkey
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Kebudi R, Amayiri N, Abedalthagafi M, Rana AN, Kirmani S, Musthaq N, Lamki ZA, Houdzi JE, Yazici H, El-Naggar S, Edwards M, Bianchi VJ, Durno C, Tabori U, Bouffet E. Position paper: Challenges and specific strategies for constitutional mismatch repair deficiency syndrome in low-resource settings. Pediatr Blood Cancer 2020; 67:e28309. [PMID: 32472748 DOI: 10.1002/pbc.28309] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Revised: 03/18/2020] [Accepted: 03/19/2020] [Indexed: 01/25/2023]
Abstract
Germline biallelic mutations in one of the mismatch repair genes, mutS homolog 2, mutS homolog 6, mutL homolog 1, or postmeiotic segregation increased 2, result in one of the most aggressive cancer syndromes in humans termed as constitutional mismatch repair deficiency (CMMRD). Individuals with CMMRD are affected with multiple tumors arising from multiple organs during childhood, and these individuals rarely reach adulthood without specific interventions. The most common tumors observed are central nervous system, hematological, and gastrointestinal malignancies. The incidence of CMMRD is expected to be high in low-resource settings due to a high rate of consanguinity in these regions, and it is thought to be underrecognized and consequently underdiagnosed. This position paper is therefore important to provide a summary of the current situation, and to highlight the necessity of increasing awareness, diagnostic criteria, and surveillance to improve survival for patients and family members.
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Affiliation(s)
- Rejin Kebudi
- Division of Pediatric Hematology-Oncology, Oncology Institute, Istanbul University, Istanbul, Turkey
| | - Nisreen Amayiri
- Department of Pediatrics, King Hussein Cancer Center, Hematology/Oncology, Amman, Jordan
| | - Malak Abedalthagafi
- Genomics Research Department, Saudi Human Genome Project, King Fahad Medical City, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia
| | - Asım Noor Rana
- Department of Pediatrics, Division of Hematology-Oncology, Dubai Hospital, Dubai, UAE
| | - Salman Kirmani
- Department of Pediatrics & Child Health, Aga Khan University, Karachi, Pakistan
| | - Naureen Musthaq
- Department of Pharmaceutical Sciences, M.M. College of Pharmacy, M.M. University, Mullana, Ambala, Haryana, India
| | - Zakiya Al Lamki
- College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Oman
| | - Jamila El Houdzi
- Hematology and Pediatric Oncology Unit, Centre d'Oncologie et d'Hematologie, Mohammed VI University Hospital, Marrakech, Morocco
| | - Hulya Yazici
- Division of Cancer Genetics, Oncology Institute, Istanbul University, Istanbul, Turkey
| | - Shahenda El-Naggar
- Tumor Biology Research Program, Department of Research, Basic Research Unit, Children's Cancer Hospital in Egypt 57357, Cairo, Egypt
| | - Melissa Edwards
- Division of Hematology-Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada
| | - Vanessa J Bianchi
- Division of Hematology-Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada
| | - Carol Durno
- The Zane Cohen Center, Mount Sinai Hospital, Toronto, Canada.,Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Uri Tabori
- Division of Hematology-Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada
| | - Eric Bouffet
- Division of Hematology-Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada
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Roberts ME, Susswein LR, Janice Cheng W, Carter NJ, Carter AC, Klein RT, Hruska KS, Marshall ML. Ancestry-specific hereditary cancer panel yields: Moving toward more personalized risk assessment. J Genet Couns 2020; 29:598-606. [PMID: 32227564 DOI: 10.1002/jgc4.1257] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 02/20/2020] [Accepted: 02/23/2020] [Indexed: 12/11/2022]
Abstract
Healthcare disparities in genomic medicine are well described. Despite some improvements, we continue to see fewer individuals of African American, Asian, and Hispanic ancestry undergo genetic counseling and testing compared to those of European ancestry. It is well established that variant of uncertain significance (VUS) rates are higher among non-European ancestral groups undergoing multi-gene hereditary cancer panel testing. However, pathogenic variant (PV) yields, and genomic data in general, are often reported in aggregate and derived from cohorts largely comprised of individuals of European ancestry. We performed a retrospective review of clinical and ancestral data for individuals undergoing multi-gene hereditary cancer panel testing to determine ancestry-specific PV and VUS rates. An ancestry other than European was reported in 29,042/104,851 (27.7%) of individuals. Compared to Europeans (9.4%), individuals of Middle Eastern ancestry were more likely to test positive for one or more pathogenic variants (12.1%, p = .0025), while African Americans were less likely (7.9%, p < .0001). Asian and Middle Eastern individuals were most likely (34.8% and 33.2%, respectively) to receive a report with an overall classification of VUS, while individuals of Ashkenazi Jewish and European ancestry were least likely (17.1% and 20.4%, respectively). These data suggest that in addition to higher VUS rates, there may be ancestry-specific PV yields. Providing aggregate data derived from cohorts saturated with European individuals does not adequately reflect genetic testing outcomes in minority groups, and interrogation of ancestry-specific data is a step toward a more personalized risk assessment.
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Affiliation(s)
| | | | - Wanchun Janice Cheng
- BioReference Laboratories, Inc., Elmwood Park, New Jersey.,Sarah Lawrence College, Genetic Counseling Program, Bronxville, New York
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Raffa L, Algethami M. Health literacy and attitudes of caregivers of intellectually disabled children towards eye care. SAUDI JOURNAL FOR HEALTH SCIENCES 2020. [DOI: 10.4103/sjhs.sjhs_215_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Kacem I, Sghaier I, Bougatef S, Nasri A, Gargouri A, Ajroud-Driss S, Gouider R. Epidemiological and clinical features of amyotrophic lateral sclerosis in a Tunisian cohort. Amyotroph Lateral Scler Frontotemporal Degener 2019; 21:131-139. [DOI: 10.1080/21678421.2019.1704012] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Affiliation(s)
- Imen Kacem
- Department of Neurology, LR18SP03, Razi Hospital, Tunis, Tunisia,
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia,
| | - Ikram Sghaier
- Department of Neurology, LR18SP03, Razi Hospital, Tunis, Tunisia,
| | - Sabrine Bougatef
- Department of Neurology, LR18SP03, Razi Hospital, Tunis, Tunisia,
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia,
| | - Amina Nasri
- Department of Neurology, LR18SP03, Razi Hospital, Tunis, Tunisia,
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia,
| | - Amina Gargouri
- Department of Neurology, LR18SP03, Razi Hospital, Tunis, Tunisia,
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia,
| | | | - Riadh Gouider
- Department of Neurology, LR18SP03, Razi Hospital, Tunis, Tunisia,
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia,
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Ben-Omran T, Al Ghanim K, Yavarna T, El Akoum M, Samara M, Chandra P, Al-Dewik N. Effects of consanguinity in a cohort of subjects with certain genetic disorders in Qatar. Mol Genet Genomic Med 2019; 8:e1051. [PMID: 31793205 PMCID: PMC6978246 DOI: 10.1002/mgg3.1051] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Revised: 08/14/2019] [Accepted: 10/01/2019] [Indexed: 12/28/2022] Open
Abstract
Background Consanguineous marriages are common in the Middle East including the Gulf countries. The rate of consanguinity in Qatar is approximately 54%, which are mainly first cousins’ marriages. Previous studies showed that consanguinity increases the prevalence of birth defects and other genetic disorders. Thus, we studied the effects of consanguinity in a cohort of subjects with certain genetic disorders in Qatar. Methods This cross‐sectional study was conducted at two centers in Qatar (Hamad Medical Corporation “HMC” and Shafallah “SC”) including 599 Qatari families with certain types of genetic and nongenetic anomalies. Results Consanguineous marriages were seen in 397 of 599 (66.2%) Qatari families and first cousin group counts for 65% in Qatari population. In the total cohort and at HMC, all consanguineous marriages had a significantly higher risk of Autosomal Recessive disorders than nonconsanguineous marriages (total cohort: odds ratio (OR) = 1.72; 95% CI: 1.10, 2.71; p = .02; HMC: OR = 2.98; 95% CI: 1.37, 6.09; p = .005). On the other hand, at HMC, nonconsanguinity was significantly related to chromosomal abnormality (OR = 6.36; 95% CI: 1.13, 35.85; p = .036). Conclusion Our data suggest a significant role of parental consanguinity in increasing the prevalence of genetic disorders; mainly Autosomal Recessive disorders. Chromosomal abnormality disorders were significantly higher among nonconsanguineous marriages. These results help better inform policy makers on social, educational, and public health initiatives that might mitigate the impact of genetic disease in the Qatari society.
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Affiliation(s)
- Tawfeg Ben-Omran
- Section of Clinical and Metabolic Genetics, Department of pediatrics, Hamad Medical Corporation, Doha, Qatar.,Department of Pediatric, Weill Cornell Medical College, Doha, Qatar.,Division of Genetic & Genomics Medicine, Sidra Medicine, Doha, Qatar
| | | | - Tarunashree Yavarna
- Section of Clinical and Metabolic Genetics, Department of pediatrics, Hamad Medical Corporation, Doha, Qatar
| | - Maha El Akoum
- Section of Clinical and Metabolic Genetics, Department of pediatrics, Hamad Medical Corporation, Doha, Qatar
| | - Muthanna Samara
- Department of Psychology, Kingston University London, London, UK
| | - Prem Chandra
- Medical Research Centre, Hamad Medical Corporation, Doha, Qatar
| | - Nader Al-Dewik
- Section of Clinical and Metabolic Genetics, Department of pediatrics, Hamad Medical Corporation, Doha, Qatar.,College of Health and Life Sciences, Hamad Bin Khalifa University (HBKU), Doha, Qatar.,Department of Pediatrics, Women's Wellness and Research Centre (WWRC), Hamad Medical Corporation, Doha, Qatar
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Kornilov SA, Tan M, Aljughaiman A, Naumova OY, Grigorenko EL. Genome-Wide Homozygosity Mapping Reveals Genes Associated With Cognitive Ability in Children From Saudi Arabia. Front Genet 2019; 10:888. [PMID: 31620175 PMCID: PMC6759945 DOI: 10.3389/fgene.2019.00888] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Accepted: 08/22/2019] [Indexed: 11/28/2022] Open
Abstract
Recent studies of the genetic foundations of cognitive ability rely on large samples (in extreme, hundreds of thousands) of individuals from relatively outbred populations of mostly European ancestry. Hypothesizing that the genetic foundation of cognitive ability depends on the broader population-specific genetic context, we performed a genome-wide association study and homozygosity mapping of cognitive ability estimates obtained through latent variable modeling in a sample of 354 children from a consanguineous population of Saudi Arabia. Approximately half of the sample demonstrated significantly elevated homozygosity levels indicative of inbreeding, and among those with elevated levels, homozygosity was negatively associated with cognitive ability. Further homozygosity mapping identified a specific run, inclusive of the GRIA4 gene, that survived corrections for multiple testing for association with cognitive ability. The results suggest that in a consanguineous population, a notable proportion of the variance in cognitive ability in the normal range in children might be regulated by population-specific mechanisms such as patterns of elevated homozygosity. This observation has implications for the field's understanding of the etiological bases of intelligence and its variability around the world.
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Affiliation(s)
- Sergey A. Kornilov
- Baylor College of Medicine, Department of Molecular and Human Genetics, Houston, TX, United States
- Department of Psychology, University of Houston, Houston, TX, USA
| | - Mei Tan
- Department of Psychology, University of Houston, Houston, TX, USA
| | | | - Oxana Yu Naumova
- Department of Psychology, University of Houston, Houston, TX, USA
- Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia
| | - Elena L. Grigorenko
- Baylor College of Medicine, Department of Molecular and Human Genetics, Houston, TX, United States
- Department of Psychology, University of Houston, Houston, TX, USA
- Child Study Center, Yale University, New Haven, CT, USA
- Moscow State University for Psychology and Education, Moscow, Russia
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Gupta T, Achari R, Chatterjee A, Chen ZP, Mehta M, Bouffet E, Jalali R. Comparison of Epidemiology and Outcomes in Neuro-Oncology Between the East and the West: Challenges and Opportunities. Clin Oncol (R Coll Radiol) 2019; 31:539-548. [PMID: 31182288 DOI: 10.1016/j.clon.2019.05.018] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 05/10/2019] [Accepted: 05/15/2019] [Indexed: 12/24/2022]
Abstract
Although neoplasms of the brain and central nervous system (CNS) are relatively uncommon, comprising only 1-2% of the overall cancer burden, they represent a substantial source of morbidity and mortality worldwide. The age-adjusted annual incidence of CNS tumours is reportedly low; however, there is substantial global variability in its incidence, with nearly a five-fold difference between regions with the highest rates in developed countries in the West and those with the lowest rates in developing countries in South-East Asia, including India, possibly attributable to key differences in environmental factors, genetic susceptibilities and cultural practices, as well as resource constraints in low-middle income countries precluding precise ascertainment and accurate diagnosis. The burden of CNS tumours is further compounded by the fact that they require highly specialised and skilled multidisciplinary care, including access to modern neuroimaging, neurosurgery, neuropathology and molecular biology, radiotherapy, chemotherapy and rehabilitation services, which may not be widely available in an integrated manner in large parts of the world with a large variation in clinical pathways, non-uniformity of care and resultant heterogeneity in clinical outcomes. CNS tumours encompass a heterogeneous spectrum of histopathological entities with differences in presentation, distinct molecular/genetic alterations, diverse biological behaviour and varying clinical outcomes. Survival is highly dependent on histology, grade and molecular biology, but varies widely across continents, even for the same tumour type and grade. In general, survival is higher in children with primary brain tumours than in adults, largely due to the differences in histological distribution across age groups. However, there is widespread variability, with 5-year survival for paediatric brain tumours being <40% in some low-middle income countries compared with 70-80% in the developed world. This review compares the descriptive epidemiology and clinical outcomes of primary brain tumours between the East and the West that pose unique challenges but also provide new opportunities in contemporary neuro-oncological practice.
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Affiliation(s)
- T Gupta
- Department of Radiation Oncology, Tata Memorial Centre, Mumbai, India.
| | - R Achari
- Department of Radiation Oncology, Tata Medical Centre, Kolkata, India
| | - A Chatterjee
- Department of Radiation Oncology, Tata Memorial Centre, Mumbai, India
| | - Z-P Chen
- Department of Neurosurgery, SunYat-sen University Cancer Centre, Guangzhou, China
| | - M Mehta
- Department of Radiation Oncology, Miami Cancer Institute, Miami, Florida, USA
| | - E Bouffet
- Neuro-Oncology Section, Division of Hematology/Oncology, Hospital for Sick Children, Toronto, Ontario, Canada
| | - R Jalali
- Department of Radiation Oncology, Apollo Proton Cancer Centre, Chennai, India
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Saeed OB, Moore MG, Zawahrah H, Tayem M, Kavoosi T, van Aalst JA. The Influence of Consanguinity on Familial Clefting Among Palestinians. Cleft Palate Craniofac J 2019; 56:1072-1079. [PMID: 30995125 DOI: 10.1177/1055665619838381] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Orofacial clefts (OFC) are the most common congenital craniofacial anomaly. The relationship between intermarriage (consanguinity) and positive family history for OFC is not well described. Consanguinity rates in developed countries are <1% but are considerably higher in the Middle East (45%). Familial clefting rates in developed countries are under 20% but in the Middle East are reported at 30% or higher. OBJECTIVE To determine OFC demographics and to clarify the relationship between consanguinity and familial clefting among Palestinians. DESIGN The Palestinian Congenial Anomalies Database is based on a 700-question survey administered to mothers of children with congenital anomalies. Orofacial clefts were diagnosed in 540 children. All demographic data were analyzed using χ2 tests with a level of significance at α < .05. RESULTS Demographics for OFC among Palestinians were similar to other published reports. Overall consanguinity rate was 53% and familial clefting rate was 49%. Parental rates of consanguinity were significantly different for patients with cleft palate. Patients with consanguineous parents had a higher rate of positive family history of clefting (67%). Recurrence of clefts in siblings was significantly higher among those born to consanguineous parents (73%) when compared to nonconsanguineous parents. CONCLUSION Consanguinity rates for Palestinians with OFC were higher than those reported in the Middle East. Familial clefting and sibling recurrence rates were also higher than expected. The risk of OFC may be mitigated with improved education about anticipated genetic consequences of consanguinity in high-risk populations such as the southern West Bank.
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Affiliation(s)
- Omar B Saeed
- 1 Ohio University Heritage College of Osteopathic Medicine, Athens, OH, USA
| | | | - H Zawahrah
- 3 Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - M Tayem
- 4 Department of Public Health, Faculty of Graduate Studies, An-Najah National University, Nablus, Occupied Palestinian Territories
| | | | - John A van Aalst
- 2 University of Cincinnati College of Medicine, OH, USA.,5 UC Department of Surgery, Cincinnati, OH, USA
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Bhinder MA, Sadia H, Mahmood N, Qasim M, Hussain Z, Rashid MM, Zahoor MY, Bhatti R, Shehzad W, Waryah AM, Jahan S. Consanguinity: A blessing or menace at population level? Ann Hum Genet 2019; 83:214-219. [PMID: 30891741 DOI: 10.1111/ahg.12308] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 02/15/2019] [Accepted: 03/01/2019] [Indexed: 12/18/2022]
Abstract
Consanguinity has highly complex and multifaceted aspects with sociocultural as well as biological debates on its pros and cons. The biological upshot of consanguinity includes the increased homozygosity, which results in manifold increased risk of genetic disorders at family and population levels. On the other hand, in addition to social, cultural, political, and economic benefits, consanguineous marriages have biological advantages at the population level. The consequence of consanguineous marriages is an upsurge in the number of homozygous diseased individuals with fewer chances of mating and reduced chances of survival, therefore evolutionarily confining the transmission of disease alleles to future generations and encouraging its elimination from a population. Protective effects of consanguinity have also been observed in a few diseases in different populations. Although attractive for many reasons, nonconsanguineous marriages will cause risk alleles to spread throughout the population, making most individuals carriers, and ultimately will resume the production of recessive diseases in subsequent generations. Although consanguinity, from an evolutionary point of view, is beneficial at the population level, it increases the risk of diseases in the very next generation. Presently, there is no treatment for most of the genetic disorders; we cannot opt for consanguinity for long-term benefits. Nonconsanguineous marriages are a better strategy by which we may delay disease manifestation for some generations until science offers a viable solution.
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Affiliation(s)
- Munir Ahmad Bhinder
- Department of Human Genetics & Molecular Biology, University of Health Sciences, Lahore, 54600, Pakistan
| | - Haleema Sadia
- Balochistan University of Information Technology, Engineering and Management Sciences, Takatu Campus, Quetta, Pakistan
| | - Nasir Mahmood
- University of Health Sciences, Lahore, 54600, Pakistan
| | - Muhammad Qasim
- Department of Bioinformatics and Biotechnology, Govt. College University, Faisalabad, Pakistan
| | - Zawar Hussain
- Department of Zoology, University of Education, Lahore, Pakistan
| | - Muhammad Mudassar Rashid
- Department of Human Genetics & Molecular Biology, University of Health Sciences, Lahore, 54600, Pakistan
| | - Muhammad Yasir Zahoor
- Institute of Biochemistry & Biotechnology, University of Veterinary & Animal Sciences, Lahore, Pakistan
| | - Rashid Bhatti
- National Centre of Excellence in Molecular Biology, Lahore, Pakistan
| | - Wasim Shehzad
- Institute of Biochemistry & Biotechnology, University of Veterinary & Animal Sciences, Lahore, Pakistan
| | - Ali Muhammad Waryah
- Molecular Biology & Genetics Department, Medical Research Center, Liaquat University of Medical & Health Sciences, Jamshoro, Pakistan
| | - Shah Jahan
- University of Health Sciences, Lahore, 54600, Pakistan
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Dargham SR, Zahirovic S, Hammoudeh M, Al Emadi S, Masri BK, Halabi H, Badsha H, Uthman I, Mahfoud ZR, Ashour H, Gad El Haq W, Bayoumy K, Kapiri M, Saxena R, Plenge RM, Kazkaz L, Arayssi T. Epidemiology and treatment patterns of rheumatoid arthritis in a large cohort of Arab patients. PLoS One 2018; 13:e0208240. [PMID: 30566451 PMCID: PMC6300286 DOI: 10.1371/journal.pone.0208240] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Accepted: 11/14/2018] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVES There is limited information on the epidemiology and treatment patterns of rheumatoid arthritis (RA) across the Arab region. We aim in this study to describe the demographic characteristics, clinical profile, and treatment patterns of patients of Arab ancestry with RA. METHODS This is a cross sectional study of 895 patients with established rheumatoid arthritis enrolled from five sites (Jordan, Lebanon, Qatar, Kingdom of Saudi Arabia (KSA), and United Arab Emirates). Demographic characteristics, clinical profile, and treatment patterns are compared between the five countries. RESULTS The majority of our patients are women, have an average disease duration of 10 years, are married and non-smokers, with completed secondary education. We report a high (>80%) ever-use of methotrexate (MTX) and steroids among our RA population, while the ever-use of disease modifying anti-rheumatic drugs (DMARDs) and TNF-inhibitors average around 67% and 33%, respectively. There are variations in RA treatment use between the five country sites. Highest utilization of steroids is identified in Jordan and KSA (p-value < 0.001), while the highest ever-use of TNF-inhibitors is reported in KSA (p-value < 0.001). CONCLUSION Disparities in usage of RA treatments among Arab patients are noted across the five countries. National gross domestic product (GDP), as well as some other unique features in each country likely affect these. Developing treatment guidelines specific to this region could contribute in delivering standardized therapies to RA patients.
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Affiliation(s)
| | | | | | | | | | - Hussein Halabi
- King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia
| | - Humeira Badsha
- Dr. Humeira Badsha Medical Center, Dubai, United Arab Emirates
| | - Imad Uthman
- American University of Beirut, Beirut, Lebanon
| | | | | | | | | | | | - Richa Saxena
- Massachusetts General Hospital, Boston, Massachusetts, United States of America
- Broad Institute, Cambridge, Massachusetts, United States of America
| | - Robert M. Plenge
- Broad Institute, Cambridge, Massachusetts, United States of America
- Merck Research Laboratories, Boston, Massachusetts, United States of America
| | | | - Thurayya Arayssi
- Weill Cornell Medicine-Qatar, Education City, Doha, Qatar
- * E-mail:
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Kemmanu V, Giliyar SK, Rao HL, Shetty BK, Kumaramanickavel G, McCarty CA. Consanguinity and its association with visual impairment in southern India: the Pavagada Pediatric Eye Disease Study 2. J Community Genet 2018; 10:345-350. [PMID: 30506417 DOI: 10.1007/s12687-018-0401-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Accepted: 11/26/2018] [Indexed: 10/27/2022] Open
Abstract
To determine the association of consanguinity with the occurrence of genetically transmitted eye diseases in rural and urban populations in Pavagada and Madhugiri taluks, Karnataka state, south India. This study was part of a population based cross-sectional prevalence survey, "The Pavagada pediatric eye disease study 2." As a part of the demographic data, trained investigators collected information on consanguinity from the parents of children identified for the study. The children underwent visual acuity measurements and were examined by an ophthalmologist. Children with minor eye diseases were treated and those with major eye diseases were seen by a pediatric ophthalmologist. Eight thousand five hundred and fifty-three children were examined. The prevalence of ocular morbidity was 6.54% and blindness was 0.09%. The percentage of consanguineously married couples in the screened population was 34.33%. Among the blind children, 75% were blind with a disease with potential genetic etiology. Out of that, 66.67% were born out of consanguineous marriage (uncle-niece). Among children with diseases with a potential genetic etiology 54.29% of the children were born out of consanguineous union. Most of these children (71.43%) were born out of uncle-niece marriages. Further analysis showed that consanguineous parents were more likely to have children with disease with a potential genetic etiology as compared to nonconsanguineous parents (odds ratio: 2.551, p = 0.012). It is evident that consanguineous marriages, especially uncle-niece unions are common in the study area. Consanguinity is more likely to result in children with eye diseases with potential genetic etiology.
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Affiliation(s)
- Vasudha Kemmanu
- Department of Pediatric Ophthalmology and Strabismus, Narayana Nethralaya, 121/C, 1st 'R' block, Rajaji Nagar, Bangalore, Karnataka, 560010, India.
| | - Subramanya K Giliyar
- Department of Pediatric Ophthalmology and Strabismus, Narayana Nethralaya, 121/C, 1st 'R' block, Rajaji Nagar, Bangalore, Karnataka, 560010, India
| | - Harsha L Rao
- Department of Pediatric Ophthalmology and Strabismus, Narayana Nethralaya, 121/C, 1st 'R' block, Rajaji Nagar, Bangalore, Karnataka, 560010, India
| | - Bhujanga K Shetty
- Department of Pediatric Ophthalmology and Strabismus, Narayana Nethralaya, 121/C, 1st 'R' block, Rajaji Nagar, Bangalore, Karnataka, 560010, India
| | - Govindasamy Kumaramanickavel
- Department of Pediatric Ophthalmology and Strabismus, Narayana Nethralaya, 121/C, 1st 'R' block, Rajaji Nagar, Bangalore, Karnataka, 560010, India
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Shakeel M, Irfan M, Khan IA. Rare genetic mutations in Pakistani patients with dilated cardiomyopathy. Gene 2018; 673:134-139. [DOI: 10.1016/j.gene.2018.06.019] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Revised: 05/23/2018] [Accepted: 06/06/2018] [Indexed: 10/14/2022]
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Kaheel H, Breß A, Hassan MA, Shah AA, Amin M, Bakhit YHY, Kniper M. Frequency of mitochondrial m.1555A > G mutation in Syrian patients with non-syndromic hearing impairment. BMC EAR, NOSE, AND THROAT DISORDERS 2018; 18:7. [PMID: 29942192 PMCID: PMC5963064 DOI: 10.1186/s12901-018-0055-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Accepted: 05/08/2018] [Indexed: 11/21/2022]
Abstract
Background Mitochondrial maternally inherited hearing impairment (HI) appears to be increasing in frequency. The incidence of mitochondrial defects causing HI is estimated to be between 6 and 33% of all hearing deficiencies. Mitochondrial m.1555A > G mutation is the first mtDNA mutation associated with non-syndromic sensorineural deafness and also with aminoglycoside induced HI. Its prevalence varied geographically between different populations. Methods We carried out PCR, restriction enzyme based screening, and sequencing of 337 subjects (including 132 patients diagnosed clinically with hereditary deafness) from 54 families from Syria for m.1555A > G mitochondrial mutation. Results Mitochondrial m.1555A > G mutation was detected in one of fifty-four families (1.85%), six out of the 132 (4.5%) of all patients with NSHI and one propositus of the 205 individuals with normal hearing (0.48%). Conclusion This is the first study to report prelingual deafness causative gene mutations identified by sequencing technology in Syrian families. It is obvious from the results that the testing for the m.1555A > G mutation is useful for diagnosis of hearing loss in Syrian patients and should also be considered prior to treatment with aminoglycosides in predisposed individuals.
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Affiliation(s)
- Hazem Kaheel
- University, HNO -universities Klink-Tubingen, Tubingen, Germany
| | - Andreas Breß
- University, HNO -universities Klink-Tubingen, Tubingen, Germany
| | - Mohamed A Hassan
- University, HNO -universities Klink-Tubingen, Tubingen, Germany.,Department of Bioinformatics, Africa city of technology, Khartoum, Sudan.,Division of Molecular Genetics, Institute of Human Genetics, University of Tübingen, Tübingen, Germany, African city of Technology, Khartoum, Sudan
| | - Aftab Ali Shah
- 3Faculty of Biotechnology, University of Malakand, Khyber Pakhtunkhwa, Pakistan
| | - Mutaz Amin
- 4Department of Biochemistry, Faculty of Medicine, University of Khartoum, P. O. Box 102, Khartoum, Sudan
| | - Yousuf H Y Bakhit
- 5Department of Basic Medical Sciences, Faculty of Dentistry-University of Khartoum, Khartoum, Sudan
| | - Marlies Kniper
- University, HNO -universities Klink-Tubingen, Tubingen, Germany
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