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Wang TT, Hirons A, Doerflinger M, Morris KV, Ledger S, Purcell DFJ, Kelleher AD, Ahlenstiel CL. Current State of Therapeutics for HTLV-1. Viruses 2024; 16:1616. [PMID: 39459949 PMCID: PMC11512412 DOI: 10.3390/v16101616] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 10/07/2024] [Accepted: 10/11/2024] [Indexed: 10/28/2024] Open
Abstract
Human T cell leukaemia virus type-1 (HTLV-1) is an oncogenic retrovirus that causes lifelong infection in ~5-10 million individuals globally. It is endemic to certain First Nations populations of Northern and Central Australia, Japan, South and Central America, Africa, and the Caribbean region. HTLV-1 preferentially infects CD4+ T cells and remains in a state of reduced transcription, often being asymptomatic in the beginning of infection, with symptoms developing later in life. HTLV-1 infection is implicated in the development of adult T cell leukaemia/lymphoma (ATL) and HTLV-1-associated myelopathies (HAM), amongst other immune-related disorders. With no preventive or curative interventions, infected individuals have limited treatment options, most of which manage symptoms. The clinical burden and lack of treatment options directs the need for alternative treatment strategies for HTLV-1 infection. Recent advances have been made in the development of RNA-based antiviral therapeutics for Human Immunodeficiency Virus Type-1 (HIV-1), an analogous retrovirus that shares modes of transmission with HTLV-1. This review highlights past and ongoing efforts in the development of HTLV-1 therapeutics and vaccines, with a focus on the potential for gene therapy as a new treatment modality in light of its successes in HIV-1, as well as animal models that may help the advancement of novel antiviral and anticancer interventions.
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Affiliation(s)
- Tiana T. Wang
- Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia; (T.T.W.); (S.L.); (A.D.K.)
| | - Ashley Hirons
- The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3052, Australia; (A.H.); (D.F.J.P.)
| | - Marcel Doerflinger
- Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia;
- Department of Medical Biology, University of Melbourne, Melbourne, VIC 3050, Australia
| | - Kevin V. Morris
- Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia;
| | - Scott Ledger
- Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia; (T.T.W.); (S.L.); (A.D.K.)
| | - Damian F. J. Purcell
- The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3052, Australia; (A.H.); (D.F.J.P.)
| | - Anthony D. Kelleher
- Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia; (T.T.W.); (S.L.); (A.D.K.)
- UNSW RNA Institute, University of New South Wales, Sydney, NSW 2052, Australia
| | - Chantelle L. Ahlenstiel
- Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia; (T.T.W.); (S.L.); (A.D.K.)
- UNSW RNA Institute, University of New South Wales, Sydney, NSW 2052, Australia
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Kapoor D, Sharma P, Saini A, Azhar E, Elste J, Kohlmeir EK, Shukla D, Tiwari V. Tunneling Nanotubes: The Cables for Viral Spread and Beyond. Results Probl Cell Differ 2024; 73:375-417. [PMID: 39242387 DOI: 10.1007/978-3-031-62036-2_16] [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] [Indexed: 09/09/2024]
Abstract
Multicellular organisms require cell-to-cell communication to maintain homeostasis and thrive. For cells to communicate, a network of filamentous, actin-rich tunneling nanotubes (TNTs) plays a pivotal role in facilitating efficient cell-to-cell communication by connecting the cytoplasm of adjacent or distant cells. Substantial documentation indicates that diverse cell types employ TNTs in a sophisticated and intricately organized fashion for both long and short-distance communication. Paradoxically, several pathogens, including viruses, exploit the structural integrity of TNTs to facilitate viral entry and rapid cell-to-cell spread. These pathogens utilize a "surfing" mechanism or intracellular transport along TNTs to bypass high-traffic cellular regions and evade immune surveillance and neutralization. Although TNTs are present across various cell types in healthy tissue, their magnitude is increased in the presence of viruses. This heightened induction significantly amplifies the role of TNTs in exacerbating disease manifestations, severity, and subsequent complications. Despite significant advancements in TNT research within the realm of infectious diseases, further studies are imperative to gain a precise understanding of TNTs' roles in diverse pathological conditions. Such investigations are essential for the development of novel therapeutic strategies aimed at leveraging TNT-associated mechanisms for clinical applications. In this chapter, we emphasize the significance of TNTs in the life cycle of viruses, showcasing the potential for a targeted approach to impede virus-host cell interactions during the initial stages of viral infections. This approach holds promise for intervention and prevention strategies.
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Affiliation(s)
- Divya Kapoor
- Department of Microbiology and Immunology, Department of Ophthalmology and Visual Sciences, University of Illinois, Chicago, IL, USA
| | - Pankaj Sharma
- Department of Microbiology and Immunology, Department of Ophthalmology and Visual Sciences, University of Illinois, Chicago, IL, USA
| | - Akash Saini
- Hinsdale Central High School, Hinsdale, IL, USA
| | - Eisa Azhar
- Department of Microbiology and Immunology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL, USA
| | - James Elste
- Department of Microbiology and Immunology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL, USA
| | | | - Deepak Shukla
- Department of Microbiology and Immunology, Department of Ophthalmology and Visual Sciences, University of Illinois, Chicago, IL, USA
| | - Vaibhav Tiwari
- Department of Microbiology and Immunology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL, USA.
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Matsuura E, Nozuma S, Dozono M, Kodama D, Tanaka M, Kubota R, Takashima H. Iliopsoas Muscle Weakness as a Key Diagnostic Marker in HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Pathogens 2023; 12:pathogens12040592. [PMID: 37111478 PMCID: PMC10143214 DOI: 10.3390/pathogens12040592] [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: 03/10/2023] [Revised: 03/31/2023] [Accepted: 04/11/2023] [Indexed: 04/29/2023] Open
Abstract
Human T-cell leukemia virus-1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a slowly progressive neurological disease that arises from HTLV-1 infection. Pathologically, the condition is characterized by diffuse myelitis, which is most evident in the thoracic spinal cord. Clinical manifestations of the infectious disease, HAM/TSP, are empirically known to include weakness of the proximal muscles of the lower extremities and atrophy of the paraspinal muscles, which is characteristic of the distribution of disturbed muscles usually seen in muscular diseases, except that the upper extremities are almost normal. This unique clinical presentation is useful information for physicians and physical therapists involved in diagnosing and rehabilitating patients with HAM/TSP, as well as critical information for understanding the pathogenesis of HAM/TSP. However, the precise pattern of muscle involvement in this condition has yet to be reported. The purpose of this study was to identify the muscles affected by HAM/TSP in order to understand the pathogenesis of HAM/TSP as well as to aid in the diagnosis and rehabilitation of HAM/TSP. A retrospective review of medical records was conducted on 101 consecutively admitted patients with HAM/TSP at Kagoshima University Hospital. Among 101 patients with HAM/TSP, all but three had muscle weakness in the lower extremities. Specifically, the hamstrings and iliopsoas muscle were the most frequently affected in over 90% of the patients. Manual muscle testing (MMT) revealed that the iliopsoas was the weakest of the muscles assessed, a consistent feature from the early to advanced stages of the disease. Our findings demonstrate a unique distribution of muscle weakness in HAM/TSP, with the proximal muscles of the lower extremities, particularly the iliopsoas muscle, being the most frequently and severely affected.
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Affiliation(s)
- Eiji Matsuura
- Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan
| | - Satoshi Nozuma
- Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan
| | - Mika Dozono
- Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan
| | - Daisuke Kodama
- Division of Neuroimmunology, Joint Research Center for Human Retrovirus Infection, Kagoshima University, Kagoshima 890-8520, Japan
| | - Masakazu Tanaka
- Division of Neuroimmunology, Joint Research Center for Human Retrovirus Infection, Kagoshima University, Kagoshima 890-8520, Japan
| | - Ryuji Kubota
- Division of Neuroimmunology, Joint Research Center for Human Retrovirus Infection, Kagoshima University, Kagoshima 890-8520, Japan
| | - Hiroshi Takashima
- Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan
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Nozuma S, Matsuura E, Tashiro Y, Nagata R, Ando M, Hiramatsu Y, Higuchi Y, Sakiyama Y, Hashiguchi A, Michizono K, Higashi K, Matsuzaki T, Kodama D, Tanaka M, Yamano Y, Moritoyo T, Kubota R, Takashima H. Efficacy of l-Arginine treatment in patients with HTLV-1-associated neurological disease. Ann Clin Transl Neurol 2022; 10:237-245. [PMID: 36547017 PMCID: PMC9930431 DOI: 10.1002/acn3.51715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 11/23/2022] [Accepted: 11/28/2022] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVE HTLV-1 infection causes HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), resulting in loss of motor function. In this Phase 2 trial, we assessed the efficacy and safety of l-arginine in patients with HAM/TSP. METHODS This open-label, single-arm, Phase 2 study enrolled patients diagnosed with HAM/TSP. Patients received l-arginine at a dose of 20 g orally for 1 week and were followed-up for 3 weeks. The primary endpoint was change in walking speed in the 10-m walk test (10MWT). The main secondary endpoints were change in Timed Up and Go Test (TUGT) time, improvement in inflammatory markers in cerebrospinal fluid (CSF), safety, and tolerability. RESULTS The study enrolled 20 patients (13 [65%] female) with a mean age of 67.8 years (95% CI 62.3 to 73.3). Although the primary endpoint, the changes in 10MWT time between baseline (Day 0) and Day 7, did not reach statistical significance (mean percent change in time -3.5%, 95% CI -10.8% to 3.7%; P = 0.32), a significant improvement was detected between baseline and Day 14 (-9.4%, 95% CI -16.6% to -2.2%; P = 0.01). Significant improvements were also observed in selected secondary endpoints, including in TUGT time (-9.1%, 95% CI -15.5% to -2.7%; P < 0.01), and in neopterin concentration in CSF (-2.1 pmol/mL, 95% CI -3.8 to -0.5; P = 0.01). Adverse events were infrequent, mild, and resolved rapidly. INTERPRETATION l-arginine therapy improved motor function and decreased CSF inflammatory markers. l-arginine thus represents a promising therapeutic option for patients with HAM/TSP. TRIAL REGISTRATION NUMBER UMIN000023854.
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Affiliation(s)
- Satoshi Nozuma
- Department of Neurology and GeriatricsKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
| | - Eiji Matsuura
- Department of Neurology and GeriatricsKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
| | - Yuichi Tashiro
- Department of Neurology and GeriatricsKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
| | - Ryusei Nagata
- Department of Neurology and GeriatricsKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
| | - Masahiro Ando
- Department of Neurology and GeriatricsKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
| | - Yu Hiramatsu
- Department of Neurology and GeriatricsKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
| | - Yujiro Higuchi
- Department of Neurology and GeriatricsKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
| | - Yusuke Sakiyama
- Department of Neurology and GeriatricsKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
| | - Akihiro Hashiguchi
- Department of Neurology and GeriatricsKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
| | - Kumiko Michizono
- Department of Neurology and GeriatricsKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
| | - Keiko Higashi
- Department of Neurology and GeriatricsKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
| | - Toshio Matsuzaki
- Division of Neuroimmunology, Joint Research Center for Human Retrovirus InfectionKagoshima UniversityKagoshimaJapan
| | - Daisuke Kodama
- Division of Neuroimmunology, Joint Research Center for Human Retrovirus InfectionKagoshima UniversityKagoshimaJapan
| | - Masakazu Tanaka
- Division of Neuroimmunology, Joint Research Center for Human Retrovirus InfectionKagoshima UniversityKagoshimaJapan
| | - Yoshihisa Yamano
- Division of Neurology, Department of Internal MedicineSt. Marianna University School of MedicineKawasakiJapan
| | - Takashi Moritoyo
- Clinical Research Promotion CenterThe University of Tokyo HospitalBunkyo‐kuJapan
| | - Ryuji Kubota
- Division of Neuroimmunology, Joint Research Center for Human Retrovirus InfectionKagoshima UniversityKagoshimaJapan
| | - Hiroshi Takashima
- Department of Neurology and GeriatricsKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
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Liberato de Matos SNF, Ladeia-Rocha G, Neto JAC, de Oliveira CJV, Neto CA, Passos L, Oliveira-Filho J, Carvalho EM. Diffusion tensor imaging metrics in diagnosis of
HTLV‐1‐associated
myelopathy. Ann Clin Transl Neurol 2022; 9:488-496. [PMID: 35263043 PMCID: PMC8994983 DOI: 10.1002/acn3.51521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/31/2022] [Accepted: 01/31/2022] [Indexed: 11/25/2022] Open
Affiliation(s)
- Sheila N F Liberato de Matos
- Immunology Service, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador.,UniFTC, Salvador, Bahia, Brazil
| | | | - José Abraão Carneiro Neto
- Immunology Service, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador
| | - Cassius J V de Oliveira
- Immunology Service, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador
| | | | - Lúcia Passos
- Immunology Service, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador
| | - Jamary Oliveira-Filho
- Neurology Service, Professor Edgard Santos University Hospital, Salvador, Bahia, Brazil.,Instituto de Ciências da Saúde, Federal University of Bahia, Salvador, Bahia, Brazil
| | - Edgar M Carvalho
- Immunology Service, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador.,Laboratório de Pesquisas Clínicas (LAPEC), Instituto Gonçalo Moniz, FIOCRUZ, Salvador, Bahia, Brazil.,National Institute of Science and Technology in Tropical Diseases (INCT-DT), CNPq, Brazil
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6
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Onisiforou A, Spyrou GM. Identification of viral-mediated pathogenic mechanisms in neurodegenerative diseases using network-based approaches. Brief Bioinform 2021; 22:bbab141. [PMID: 34237135 PMCID: PMC8574625 DOI: 10.1093/bib/bbab141] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 03/01/2021] [Accepted: 03/23/2021] [Indexed: 12/18/2022] Open
Abstract
During the course of a viral infection, virus-host protein-protein interactions (PPIs) play a critical role in allowing viruses to replicate and survive within the host. These interspecies molecular interactions can lead to viral-mediated perturbations of the human interactome causing the generation of various complex diseases. Evidences suggest that viral-mediated perturbations are a possible pathogenic etiology in several neurodegenerative diseases (NDs). These diseases are characterized by chronic progressive degeneration of neurons, and current therapeutic approaches provide only mild symptomatic relief; therefore, there is unmet need for the discovery of novel therapeutic interventions. In this paper, we initially review databases and tools that can be utilized to investigate viral-mediated perturbations in complex NDs using network-based analysis by examining the interaction between the ND-related PPI disease networks and the virus-host PPI network. Afterwards, we present our theoretical-driven integrative network-based bioinformatics approach that accounts for pathogen-genes-disease-related PPIs with the aim to identify viral-mediated pathogenic mechanisms focusing in multiple sclerosis (MS) disease. We identified seven high centrality nodes that can act as disease communicator nodes and exert systemic effects in the MS-enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways network. In addition, we identified 12 KEGG pathways, 5 Reactome pathways and 52 Gene Ontology Immune System Processes by which 80 viral proteins from eight viral species might exert viral-mediated pathogenic mechanisms in MS. Finally, our analysis highlighted the Th17 differentiation pathway, a disease communicator node and part of the 12 underlined KEGG pathways, as a key viral-mediated pathogenic mechanism and a possible therapeutic target for MS disease.
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Affiliation(s)
- Anna Onisiforou
- Department of Bioinformatics, Cyprus Institute of Neurology & Genetics, and the Cyprus School of Molecular Medicine, Cyprus
| | - George M Spyrou
- Department of Bioinformatics, Cyprus Institute of Neurology & Genetics, and professor at the Cyprus School of Molecular Medicine, Cyprus
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7
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Tiwari V, Koganti R, Russell G, Sharma A, Shukla D. Role of Tunneling Nanotubes in Viral Infection, Neurodegenerative Disease, and Cancer. Front Immunol 2021; 12:680891. [PMID: 34194434 PMCID: PMC8236699 DOI: 10.3389/fimmu.2021.680891] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 05/26/2021] [Indexed: 12/14/2022] Open
Abstract
The network of tunneling nanotubes (TNTs) represents the filamentous (F)-actin rich tubular structure which is connected to the cytoplasm of the adjacent and or distant cells to mediate efficient cell-to-cell communication. They are long cytoplasmic bridges with an extraordinary ability to perform diverse array of function ranging from maintaining cellular physiology and cell survival to promoting immune surveillance. Ironically, TNTs are now widely documented to promote the spread of various pathogens including viruses either during early or late phase of their lifecycle. In addition, TNTs have also been associated with multiple pathologies in a complex multicellular environment. While the recent work from multiple laboratories has elucidated the role of TNTs in cellular communication and maintenance of homeostasis, this review focuses on their exploitation by the diverse group of viruses such as retroviruses, herpesviruses, influenza A, human metapneumovirus and SARS CoV-2 to promote viral entry, virus trafficking and cell-to-cell spread. The later process may aggravate disease severity and the associated complications due to widespread dissemination of the viruses to multiple organ system as observed in current coronavirus disease 2019 (COVID-19) patients. In addition, the TNT-mediated intracellular spread can be protective to the viruses from the circulating immune surveillance and possible neutralization activity present in the extracellular matrix. This review further highlights the relevance of TNTs in ocular and cardiac tissues including neurodegenerative diseases, chemotherapeutic resistance, and cancer pathogenesis. Taken together, we suggest that effective therapies should consider precise targeting of TNTs in several diseases including virus infections.
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Affiliation(s)
- Vaibhav Tiwari
- Department of Microbiology & Immunology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL, United States
| | - Raghuram Koganti
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, United States
| | - Greer Russell
- Department of Biomedical Sciences, College of Graduate Studies, Midwestern University, Downers Grove, IL, United States
| | - Ananya Sharma
- Vanderbilt University School of Medicine, Nashville, TN, United States
| | - Deepak Shukla
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, United States.,Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL, United States
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Xiao XW, Du J, Jiao B, Liao XX, Zhou L, Liu XX, Yuan ZH, Guo LN, Wang X, Shen L, Lin ZY. Novel ATL1 mutation in a Chinese family with hereditary spastic paraplegia: A case report and review of literature. World J Clin Cases 2019; 7:1358-1366. [PMID: 31236401 PMCID: PMC6580333 DOI: 10.12998/wjcc.v7.i11.1358] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 03/23/2019] [Accepted: 04/09/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Hereditary spastic paraplegias (HSPs) refer to a group of heterogeneous neurodegenerative diseases characterized by lower limbs spasticity and weakness. So far, over 72 genes have been found to cause HSP (SPG1-SPG72). Among autosomal dominant HSP patients, spastic paraplegia 4 (SPG4/SPAST) gene is the most common pathogenic gene, and atlastin-1 (ATL1) is the second most common one. Here we reported a novel ATL1 mutation in a Chinese spastic paraplegia 3A (SPG3A) family, which expands the clinical and genetic spectrum of ATL1 mutations.
CASE SUMMARY A 9-year-old boy with progressive spastic paraplegia accompanied by right hearing loss and mental retardation for five years was admitted to our hospital. Past history was unremarkable. The family history was positive, and his grandfather and mother had similar symptoms. Neurological examinations revealed hypermyotonia in his lower limbs, hyperreflexia in knee reflex, bilateral positive Babinski signs and scissors gait. The results of blood routine test, liver function test, blood glucose test, ceruloplasmin test and vitamin test were all normal. The serum lactic acid level was significantly increased. The testing for brainstem auditory evoked potential demonstrated that the right side hearing was impaired while the left was normal. Magnetic resonance imaging showed mild atrophy of the spinal cord. The gene panel test revealed that the proband carried an ATL1 c.752A>G p.Gln251Arg (p.Q251R) mutation, and Sanger sequencing confirmed the existence of family co-segregation.
CONCLUSION We reported a novel ATL1 Q251R mutation and a novel clinical phenotype of hearing loss in a Chinese SPG3A family.
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Affiliation(s)
- Xue-Wen Xiao
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Juan Du
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Bin Jiao
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha 410008, Hunan Province, China
| | - Xin-Xin Liao
- Department of Geriatrics Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Lu Zhou
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Xi-Xi Liu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Zhen-Hua Yuan
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Li-Na Guo
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Xin Wang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Lu Shen
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha 410008, Hunan Province, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha 410008, Hunan Province, China
| | - Zhang-Yuan Lin
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
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9
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Finsterer J, Löscher WN, Wanschitz J, Quasthoff S, Grisold W. Secondary myopathy due to systemic diseases. Acta Neurol Scand 2016; 134:388-402. [PMID: 26915593 PMCID: PMC7159623 DOI: 10.1111/ane.12576] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/09/2016] [Indexed: 12/27/2022]
Abstract
Background Some systemic diseases also affect the skeletal muscle to various degrees and with different manifestations. This review aimed at summarizing and discussing recent advances concerning the management of muscle disease in systemic diseases. Method Literature review by search of MEDLINE, and Current Contents with appropriate search terms. Results Secondary muscle disease occurs in infectious disease, endocrine disorders, metabolic disorders, immunological disease, vascular diseases, hematological disorders, and malignancies. Muscle manifestations in these categories include pathogen‐caused myositis, muscle infarction, rhabdomyolysis, myasthenia, immune‐mediated myositis, necrotising myopathy, or vasculitis‐associated myopathy. Muscle affection may concern only a single muscle, a group of muscles, or the entire musculature. Severity of muscle affection may be transient or permanent, may be a minor part of or may dominate the clinical picture, or may be mild or severe, requiring invasive measures including artificial ventilation if the respiratory muscles are additionally involved. Diagnostic work‐up is similar to that of primary myopathies by application of non‐invasive and invasive techniques. Treatment of muscle involvement in systemic diseases is based on elimination of the underlying cause and supportive measures. The prognosis is usually fair if the causative disorder is effectively treatable but can be fatal in single cases if the entire musculature including the respiratory muscles is involved, in case of infection, or in case of severe rhabdomyolysis. Conclusion Secondary muscle manifestations of systemic diseases must be addressed and appropriately managed. Prognosis of secondary muscle disease in systemic diseases is usually fair if the underlying condition is accessible to treatment.
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Affiliation(s)
| | - W. N. Löscher
- Department of Neurology; Medical University of Innsbruck; Innsbruck Austria
| | - J. Wanschitz
- Department of Neurology; Medical University of Innsbruck; Innsbruck Austria
| | - S. Quasthoff
- Department of Neurology; Graz Medical University; Graz Austria
| | - W. Grisold
- Department of Neurology; Kaiser-Franz-Josef Spital; Vienna Austria
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