|
1
|
Yammine KM, Mirda Abularach S, Kim SY, Bikovtseva AA, Lilianty J, Butty VL, Schiavoni RP, Bateman JF, Lamandé SR, Shoulders MD. ER procollagen storage defect without coupled unfolded protein response drives precocious arthritis. Life Sci Alliance 2024; 7:e202402842. [PMID: 38981683 PMCID: PMC11234256 DOI: 10.26508/lsa.202402842] [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: 05/28/2024] [Revised: 06/21/2024] [Accepted: 06/26/2024] [Indexed: 07/11/2024] Open
Abstract
Collagenopathies are a group of clinically diverse disorders caused by defects in collagen folding and secretion. For example, mutations in the gene encoding collagen type-II, the primary collagen in cartilage, can lead to diverse chondrodysplasias. One example is the Gly1170Ser substitution in procollagen-II, which causes precocious osteoarthritis. Here, we biochemically and mechanistically characterize an induced pluripotent stem cell-based cartilage model of this disease, including both hetero- and homozygous genotypes. We show that Gly1170Ser procollagen-II is notably slow to fold and secrete. Instead, procollagen-II accumulates intracellularly, consistent with an endoplasmic reticulum (ER) storage disorder. Likely owing to the unique features of the collagen triple helix, this accumulation is not recognized by the unfolded protein response. Gly1170Ser procollagen-II interacts to a greater extent than wild-type with specific ER proteostasis network components, consistent with its slow folding. These findings provide mechanistic elucidation into the etiology of this disease. Moreover, the easily expandable cartilage model will enable rapid testing of therapeutic strategies to restore proteostasis in the collagenopathies.
Collapse
Affiliation(s)
- Kathryn M Yammine
- Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA
| | | | - Seo-Yeon Kim
- Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Agata A Bikovtseva
- Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Jinia Lilianty
- Murdoch Children's Research Institute, Parkville, Australia
- Department of Paediatrics, University of Melbourne, Parkville, Australia
| | - Vincent L Butty
- BioMicro Center, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Richard P Schiavoni
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - John F Bateman
- Murdoch Children's Research Institute, Parkville, Australia
- Department of Paediatrics, University of Melbourne, Parkville, Australia
| | - Shireen R Lamandé
- Murdoch Children's Research Institute, Parkville, Australia
- Department of Paediatrics, University of Melbourne, Parkville, Australia
- The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Murdoch Children's Research Institute, Parkville, Australia
| | - Matthew D Shoulders
- Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
| |
Collapse
|
|
2
|
Yammine KM, Abularach SM, Kim SY, Bikovtseva AA, Lilianty J, Butty VL, Schiavoni RP, Bateman JF, Lamandé SR, Shoulders MD. ER procollagen storage defect without coupled unfolded protein response drives precocious arthritis. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2023.10.19.562780. [PMID: 37905055 PMCID: PMC10614947 DOI: 10.1101/2023.10.19.562780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/02/2023]
Abstract
Collagenopathies are a group of clinically diverse disorders caused by defects in collagen folding and secretion. For example, mutations in the gene encoding collagen type-II, the primary collagen in cartilage, can lead to diverse chondrodysplasias. One example is the Gly1170Ser substitution in procollagen-II, which causes precocious osteoarthritis. Here, we biochemically and mechanistically characterize an induced pluripotent stem cell-based cartilage model of this disease, including both hetero- and homozygous genotypes. We show that Gly1170Ser procollagen-II is notably slow to fold and secrete. Instead, procollagen-II accumulates intracellularly, consistent with an endoplasmic reticulum (ER) storage disorder. Owing to unique features of the collagen triple helix, this accumulation is not recognized by the unfolded protein response. Gly1170Ser procollagen-II interacts to a greater extent than wild-type with specific proteostasis network components, consistent with its slow folding. These findings provide mechanistic elucidation into the etiology of this disease. Moreover, the cartilage model will enable rapid testing of therapeutic strategies to restore proteostasis in the collagenopathies.
Collapse
|
|
3
|
Bian Y, Hu T, Lv Z, Xu Y, Wang Y, Wang H, Zhu W, Feng B, Liang R, Tan C, Weng X. Bone tissue engineering for treating osteonecrosis of the femoral head. EXPLORATION (BEIJING, CHINA) 2023; 3:20210105. [PMID: 37324030 PMCID: PMC10190954 DOI: 10.1002/exp.20210105] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 05/12/2022] [Indexed: 06/16/2023]
Abstract
Osteonecrosis of the femoral head (ONFH) is a devastating and complicated disease with an unclear etiology. Femoral head-preserving surgeries have been devoted to delaying and hindering the collapse of the femoral head since their introduction in the last century. However, the isolated femoral head-preserving surgeries cannot prevent the natural progression of ONFH, and the combination of autogenous or allogeneic bone grafting often leads to many undesired complications. To tackle this dilemma, bone tissue engineering has been widely developed to compensate for the deficiencies of these surgeries. During the last decades, great progress has been made in ingenious bone tissue engineering for ONFH treatment. Herein, we comprehensively summarize the state-of-the-art progress made in bone tissue engineering for ONFH treatment. The definition, classification, etiology, diagnosis, and current treatments of ONFH are first described. Then, the recent progress in the development of various bone-repairing biomaterials, including bioceramics, natural polymers, synthetic polymers, and metals, for treating ONFH is presented. Thereafter, regenerative therapies for ONFH treatment are also discussed. Finally, we give some personal insights on the current challenges of these therapeutic strategies in the clinic and the future development of bone tissue engineering for ONFH treatment.
Collapse
Affiliation(s)
- Yixin Bian
- Department of Orthopedic SurgeryState Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina
| | - Tingting Hu
- State Key Laboratory of Chemical Resource EngineeringBeijing Advanced Innovation Center for Soft Matter Science and EngineeringBeijing University of Chemical TechnologyBeijingChina
| | - Zehui Lv
- Department of Orthopedic SurgeryState Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina
| | - Yiming Xu
- Department of Orthopedic SurgeryState Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina
| | - Yingjie Wang
- Department of Orthopedic SurgeryState Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina
| | - Han Wang
- Department of Orthopedic SurgeryState Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina
| | - Wei Zhu
- Department of Orthopedic SurgeryState Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina
| | - Bin Feng
- Department of Orthopedic SurgeryState Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina
| | - Ruizheng Liang
- State Key Laboratory of Chemical Resource EngineeringBeijing Advanced Innovation Center for Soft Matter Science and EngineeringBeijing University of Chemical TechnologyBeijingChina
| | - Chaoliang Tan
- Department of ChemistryCity University of Hong KongKowloonHong Kong SARChina
| | - Xisheng Weng
- Department of Orthopedic SurgeryState Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina
| |
Collapse
|
|
4
|
Zhang Z, Zhu K, Dai H, Wang Q, Zhang C, Zhang Z. A novel mutation of COL2A1 in a large Chinese family with avascular necrosis of the femoral head. BMC Med Genomics 2021; 14:147. [PMID: 34088323 PMCID: PMC8178877 DOI: 10.1186/s12920-021-00995-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Accepted: 05/27/2021] [Indexed: 12/05/2022] Open
Abstract
Avascular necrosis of the femoral head (ANFH) is a debilitating bone disease, characterized by collapse of the femoral head and subsequent loss of hip joint function. Heterozygous mutations in COL2A1 have been identified to cause familial ANFH. Here we report on a large Chinese family with ANFH and a novel heterozygous mutation (c.3517 G > A, p.Gly1173Ser) in exon 50 of COL2A1 in the Gly-X-Y domain. Previously, only five different COL2A1 mutations have been described in patients with familial ANFH. Therefore, our findings provide significant clues to the phenotype-genotype relationships in familial ANFH and may be helpful in clinical diagnosis. Furthermore, these results should assist further studies of the mechanisms underlying collagen diseases.
Collapse
Affiliation(s)
- Zeng Zhang
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated the Sixth People's Hospital, 600 Yi-Shan Rd., Shanghai, 200233, People's Republic of China
| | - Kechao Zhu
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated the Sixth People's Hospital, 600 Yi-Shan Rd., Shanghai, 200233, People's Republic of China
| | - Huiyong Dai
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated the Sixth People's Hospital, 600 Yi-Shan Rd., Shanghai, 200233, People's Republic of China
| | - Qi Wang
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated the Sixth People's Hospital, 600 Yi-Shan Rd., Shanghai, 200233, People's Republic of China.
| | - Changqing Zhang
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated the Sixth People's Hospital, 600 Yi-Shan Rd., Shanghai, 200233, People's Republic of China
| | - Zhenlin Zhang
- Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated the Sixth People's Hospital, 600 Yi-Shan Rd., Shanghai, 200233, People's Republic of China
| |
Collapse
|
|
5
|
Ando W, Sakai T, Fukushima W, Kaneuji A, Ueshima K, Yamasaki T, Yamamoto T, Nishii T, Sugano N. Japanese Orthopaedic Association 2019 Guidelines for osteonecrosis of the femoral head. J Orthop Sci 2021; 26:46-68. [PMID: 33388233 DOI: 10.1016/j.jos.2020.06.013] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 06/04/2020] [Accepted: 06/05/2020] [Indexed: 12/20/2022]
Abstract
PURPOSE The Clinical Practice Guidelines for Osteonecrosis of the Femoral Head (ONFH) 2019 Edition, written by the working group for ONFH guidelines of the Japanese Investigation Committee (JIC) for ONFH under the auspices of the Japanese Ministry of Health, Labour, and Welfare and endorsed by the Japanese Orthopaedic Association, were published in Japanese in October 2019. The objective of this guideline is to provide a support tool for decision-making between doctors and patients. METHODS Procedures for developing this guideline were based on the Medical Information Network Distribution Service Handbook for Clinical Practice Guideline Development 2014, which proposed an appropriate method for preparing clinical guidelines in Japan. RESULTS This clinical practice guideline consists of 7 chapters: epidemiology; pathology; diagnosis; conservative therapy; surgical treatment: bone transplantation/cell therapy; surgical treatment: osteotomy; and surgical treatment: hip replacement. Twelve background questions and 13 clinical questions were determined to define the basic features of the disease and to be addressed when deciding treatment in daily practice, respectively. CONCLUSIONS The clinical practice guidelines for the ONFH 2019 edition will be useful for physicians, investigators, and medical staff in clinical practice, as well as for patients, during the decision-making process when defining how to treat ONFH.
Collapse
Affiliation(s)
- Wataru Ando
- Department of Orthopaedic Medical Engineering, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Takashi Sakai
- Department of Orthopedic Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Wakaba Fukushima
- Department of Public Health, Osaka City University Graduate School of Medicine, Osaka, Osaka, Japan
| | - Ayumi Kaneuji
- Department of Orthopaedic Surgery, Kanazawa Medical University, Kahoku-gun, Ishikawa, Japan
| | - Keiichiro Ueshima
- Department of Orthopaedic Surgery, Kyoto Interdisciplinary Institute Hospital of Community Medicine, Kyoto, Kyoto, Japan
| | - Takuma Yamasaki
- Department of Orthopaedic Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Hiroshima, Japan
| | - Takuaki Yamamoto
- Department of Orthopaedic Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Fukuoka, Japan
| | - Takashi Nishii
- Department of Orthopaedic Surgery, Osaka General Medical Center, Osaka, Osaka, Japan
| | | | - Nobuhiko Sugano
- Department of Orthopaedic Medical Engineering, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
| |
Collapse
|
|
6
|
Guo Y, Cao Y, Gong S, Zhang S, Hou F, Zhang X, Hu J, Yang Z, Yi J, Luo D, Chen X, Song J. Correlation analysis between CARMEN variants and alcohol-induced osteonecrosis of the femoral head in the Chinese population. BMC Musculoskelet Disord 2020; 21:547. [PMID: 32799824 PMCID: PMC7429464 DOI: 10.1186/s12891-020-03553-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Accepted: 07/31/2020] [Indexed: 01/18/2023] Open
Abstract
Background Osteonecrosis of the femoral head (ONFH) is a complicated disease associated with trauma, hormone abuse and excessive alcohol consumption. Polymorphisms of long non-coding RNAs have been also linked with the development of ONFH. Our research aimed to explore the relationship between CARMEN (Cardiac Mesoderm Enhancer-Associated Non-Coding RNA) variants and ONFH risk. Methods Our study used Agena MassARRAY Assay to genotype 6 selected single nucleotide polymorphisms (SNPs) in 731 participants (308 alcohol-induced ONFH patients and 423 controls). We used odds ratios (ORs) and 95% confidence intervals (CIs) to calculate the effect of gene polymorphisms on the occurrence of alcohol-induced ONFH by logistic regression analysis and haplotype analysis. Results Our overall analysis illustrated that rs13177623 and rs12654195 had an association with a reduced risk of ONFH after adjustment for age and gender. We also found that rs13177623, rs12654195 and rs11168100 were associated with a decreased susceptibility to alcohol-induced ONFH in people ≤45 years. In addition, the necrotic sites stratification analysis showed that rs12654195 was only found to be related to alcohol-induced ONFH risk in the recessive model. In patients with different clinical stages, rs353300 was observed to be associated with a higher incidence of ONFH. Individuals with different genotypes of rs13177623, rs12654195 and rs11168100 had significantly different clinical parameters (cholinesterase, globulin, percentage of neutrophils and the absolute value of lymphocytes). Conclusions Our data provided new light on the association between CARMEN polymorphisms and alcohol-induced ONFH risk in the Chinese Han population.
Collapse
Affiliation(s)
- Yongchang Guo
- Department of Orthopedics, Zhengzhou Traditional Chinese Hospital of Orthopaedics, #1226 East Hanghang Road, Zhengzhou, 450000, Henan, China
| | - Yuju Cao
- Department of Orthopedics, Zhengzhou Traditional Chinese Hospital of Orthopaedics, #1226 East Hanghang Road, Zhengzhou, 450000, Henan, China.
| | - Shunguo Gong
- Department of Orthopedics, Zhengzhou Traditional Chinese Hospital of Orthopaedics, #1226 East Hanghang Road, Zhengzhou, 450000, Henan, China
| | - Sumei Zhang
- Department of Orthopedics, Zhengzhou Traditional Chinese Hospital of Orthopaedics, #1226 East Hanghang Road, Zhengzhou, 450000, Henan, China
| | - Fengzhi Hou
- Department of Orthopedics, Zhengzhou Traditional Chinese Hospital of Orthopaedics, #1226 East Hanghang Road, Zhengzhou, 450000, Henan, China
| | - Xinjie Zhang
- Department of Orthopedics, Zhengzhou Traditional Chinese Hospital of Orthopaedics, #1226 East Hanghang Road, Zhengzhou, 450000, Henan, China
| | - Jiangeng Hu
- Department of Orthopedics, Zhengzhou Traditional Chinese Hospital of Orthopaedics, #1226 East Hanghang Road, Zhengzhou, 450000, Henan, China
| | - Zhimin Yang
- Department of Orthopedics, Zhengzhou Traditional Chinese Hospital of Orthopaedics, #1226 East Hanghang Road, Zhengzhou, 450000, Henan, China
| | - Juanjuan Yi
- Department of Orthopedics, Zhengzhou Traditional Chinese Hospital of Orthopaedics, #1226 East Hanghang Road, Zhengzhou, 450000, Henan, China
| | - Dan Luo
- Department of Orthopedics, Zhengzhou Traditional Chinese Hospital of Orthopaedics, #1226 East Hanghang Road, Zhengzhou, 450000, Henan, China
| | - Xifeng Chen
- Department of Orthopedics, Zhengzhou Traditional Chinese Hospital of Orthopaedics, #1226 East Hanghang Road, Zhengzhou, 450000, Henan, China
| | - Jingbo Song
- Department of Orthopedics, Zhengzhou Traditional Chinese Hospital of Orthopaedics, #1226 East Hanghang Road, Zhengzhou, 450000, Henan, China
| |
Collapse
|
|
7
|
Sun HS, Yang QR, Bai YY, Hu NW, Liu DX, Qin CY. Gene testing for osteonecrosis of the femoral head in systemic lupus erythematosus using targeted next-generation sequencing: A pilot study. World J Clin Cases 2020; 8:2530-2541. [PMID: 32607330 PMCID: PMC7322418 DOI: 10.12998/wjcc.v8.i12.2530] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 05/09/2020] [Accepted: 05/18/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Previous publications indicated that genetic predisposition might play important roles in the onset of osteonecrosis of the femoral head (ONFH) in systemic lupus erythematosus (SLE). Some gene loci such as complement C3d receptor 2 (CR2), nitric oxide synthase 3 (NOS3), collagen type II alpha 1 chain (COL2A1), protein tyrosine phosphatase non-receptor type 22 (PTPN22), and transient receptor potential cation channel subfamily V member 4 (TRPV4) were reported to be involved in this process.
AIM To investigate whether the risk of ONFH in SLE is associated with single nucleotide variations (SNVs) in these five genes.
METHODS SNVs in the CR2, NOS3, COL2A1, PTPN22, and TRPV4 genes were examined by using FastTarget and Illumina Miseq sequencing technologies in 49 cases of SLE with ONFH. Burrows–wheeler aligner was used to align the sequencing reads to hg19, and GATK and Varscan programs were used to perform SNV calling. PolyPhen-2, SIFT, and MutationTaster were used to assess the functional effects of non-synonymous SNVs.
RESULTS Six of the 49 patients were confirmed to have low frequency SNVs, including one patient with SNVs in NOS3 (exon 6: c.814G>A: p.E272K and exon 7: c.814G>A: p.E272K.), four in COL2A1 (rs41263847: exon 29: c.1913C>T: p.T638I, exon 28: c.1706C>T: p.T569I, and rs371445823: exon 8: c.580G>A: p.A194T, exon 7: c.373G>A: p.A125T), and one in CR2 (rs45573035: exon 2: c.200C>G: p.T67S).
CONCLUSION The onset of ONFH in SLE might be associated with the identified SNVs in NOS3, COL2A1, and CR2.
Collapse
Affiliation(s)
- Hong-Sheng Sun
- Department of Rheumatology and Immunology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
| | - Qing-Rui Yang
- Department of Rheumatology and Immunology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
| | - Yan-Yan Bai
- Department of Rheumatology and Immunology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
| | - Nai-Wen Hu
- Department of Rheumatology and Immunology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
| | - Dong-Xia Liu
- Department of Rheumatology and Immunology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
| | - Cheng-Yong Qin
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
| |
Collapse
|
|
8
|
Zhang B, Zhang Y, Wu N, Li J, Liu H, Wang J. Integrated analysis of COL2A1 variant data and classification of type II collagenopathies. Clin Genet 2019; 97:383-395. [PMID: 31758797 DOI: 10.1111/cge.13680] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Revised: 11/18/2019] [Accepted: 11/20/2019] [Indexed: 11/29/2022]
Abstract
The COL2A1 gene encodes the alpha-1 chain of type II procollagen. Type II collagen, comprised of three identical alpha-1 chains, is the major component of cartilage. COL2A1 gene variants are the etiologies of genetic diseases, termed type II collagenopathies, with a wide spectrum of clinical presentations. To date, at least 460 distinct COL2A1 mutations, identified in 663 independent probands, and 21 definite disorders have been reported. Nevertheless, a well-defined genotype-phenotype correlation has not been established, and few hot spots of mutation have been reported. In this study, we analyzed data of COL2A1 variants and clinical information of patients obtained from the Leiden Open Variation Database 3.0, as well as the currently available relevant literature. We determined the characteristics of the COL2A1 variants and distributions of the clinical manifestations in patients, and identified four likely genotype-phenotype correlations. Moreover, we classified 21 COL2A1-related disorders into five categories, which may assist clinicians in understanding the essence of these complex phenotypes and prompt genetic screening in clinical practice.
Collapse
Affiliation(s)
- Boyan Zhang
- Orthopedic Medical Center, The Second Hospital of Jilin University, Changchun, China
| | - Yue Zhang
- Department of Radiation Oncology, First Bethune Hospital of Jilin University, Changchun, China
| | - Naichao Wu
- Orthopedic Medical Center, The Second Hospital of Jilin University, Changchun, China
| | - Jianing Li
- Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, China
| | - He Liu
- Orthopedic Medical Center, The Second Hospital of Jilin University, Changchun, China
| | - Jincheng Wang
- Orthopedic Medical Center, The Second Hospital of Jilin University, Changchun, China
| |
Collapse
|
|
9
|
Zhao X, Yang F, Sun L, Zhang A. Association between NOS3 polymorphisms and osteonecrosis of the femoral head. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2019; 47:1423-1427. [PMID: 31007072 DOI: 10.1080/21691401.2019.1593995] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Xiaodong Zhao
- Department of Orthopaedics, Weifang Traditional Chinese Hospital, Weifang, China
| | - Fuqiang Yang
- Department of Orthopaedics, Eighty-ninth Hospital of the Chinese People’s Liberation Army, Weifang, China
| | - Luwei Sun
- Department of Orthopaedics, Weifang Traditional Chinese Hospital, Weifang, China
| | - Ali Zhang
- Department of Orthopaedics, Eighty-ninth Hospital of the Chinese People’s Liberation Army, Weifang, China
| |
Collapse
|
|
10
|
Liu F, Xiong Z, Liu Q, Hu J, Li W, Zhang N. COL2A1 mutation (c.3508G>A) leads to avascular necrosis of the femoral head in a Chinese family: A case report. Mol Med Rep 2018; 18:254-260. [PMID: 29750297 PMCID: PMC6059677 DOI: 10.3892/mmr.2018.8984] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2017] [Accepted: 03/08/2018] [Indexed: 01/13/2023] Open
Abstract
Avascular necrosis of the femoral head (ANFH) is a consequence of ischemia. Although the majority of cases of ANFH are sporadic, certain familial cases of ANFH have been reported to be associated with collagen type II α1 chain (COL2A1) mutations, which lead to COL2A1 gene dysfunction. The structure of secreted type II collagen contains a core area with a triple helical glycine (Gly)-X-Y domain, and the replacement of Gly in this region as a result of COL2A1 mutations may damage the structure of type II collagen. In the present study, a Chinese family with ANFH was recruited and genetic analysis was conducted to determine whether COL2A1 mutations were implicated in this familial ANFH. A three-generation family containing 31 members, as well as 20 patients with sporadic ANFH, were recruited for investigation. The diagnosis was performed by independent surgeons and radiologists according to internationally recognized criteria. In the present study, a heterozygous c.3508G>A mutation in exon 50 of the COL2A1 gene was identified, which results in the substitution of Gly with serine at codon 1,170. Furthermore, genetic pedigree analysis indicated that this mutation was inherited in an autosomal dominant manner. The present study revealed that a heterozygous c.3508G>A mutation in the COL2A1 gene was involved in ANFH development in one Chinese family. Therefore, it is proposed that individuals who carry this c.3508G>A mutation in the COL2A1 gene should receive genetic counseling and early intervention for ANFH.
Collapse
Affiliation(s)
- Fang Liu
- Department of Orthopedics, Second Hospital of Yueyang, Yueyang, Hunan 414000, P.R. China
| | - Zhizheng Xiong
- Department of Orthopedics, Second Hospital of Yueyang, Yueyang, Hunan 414000, P.R. China
| | - Qi Liu
- Department of Orthopedics, Second Hospital of Yueyang, Yueyang, Hunan 414000, P.R. China
| | - Jinxi Hu
- Department of Orthopedics, Second Hospital of Yueyang, Yueyang, Hunan 414000, P.R. China
| | - Wenhua Li
- Department of Orthopedics, Second Hospital of Yueyang, Yueyang, Hunan 414000, P.R. China
| | - Na Zhang
- Department of Orthopedics, Second Hospital of Yueyang, Yueyang, Hunan 414000, P.R. China
| |
Collapse
|
|
11
|
Sakamoto Y, Yamamoto T, Miyake N, Matsumoto N, Iida A, Nakashima Y, Iwamoto Y, Ikegawa S. Screening of the COL2A1 mutation in idiopathic osteonecrosis of the femoral head. J Orthop Res 2017; 35:768-774. [PMID: 27183340 DOI: 10.1002/jor.23300] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2016] [Accepted: 05/11/2016] [Indexed: 02/04/2023]
Abstract
Idiopathic osteonecrosis of the femoral head (idiopathic ONFH) is an ischemic disorder resulting in necrosis of the subchondral bone of the femoral head. COL2A1 mutations, including c.3508G>A, have been reported to be involved in its etiology. However, the etiological role of COL2A1 mutations in idiopathic ONFH remains controversial, because the pathology of idiopathic ONFH is ischemic necrosis, not epiphyseal dysplasia usually seen in the diseases caused by COL2A1 mutations. The purpose of this study is to examine whether COL2A1 mutations have causal relation with idiopathic ONFH or not. We recruited 1,451 Japanese patients with idiopathic ONFH, including steroid-, alcohol-, and neither steroid nor alcohol-associated (neither-associated) ONFH. The diagnosis was based on the criteria of the Japanese Research Committee on idiopathic ONFH of the Ministry of Health, Labour and Welfare. By whole-exome sequencing, entire COL2A1 coding regions and flanking introns were analyzed in 49 neither-associated ONFH patients. In addition, the c.3508G>A mutation of COL2A1 was checked in all idiopathic ONFH patients using the invader assay. Whole-exome sequencing did not detect any COL2A1 mutations in the 49 patients. The c.3508G>A mutation was not found in any of the 1,451 patients. In conclusion, COL2A1 is unlikely to cause idiopathic ONFH. Epiphyseal dysplasia of the femoral head caused by COL2A1 mutations may radiographically mimic idiopathic ONFH. COL2A1 mutations should prompt clinical re-evaluation of the patient's phenotype. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:768-774, 2017.
Collapse
Affiliation(s)
- Yuma Sakamoto
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.,Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan
| | - Takuaki Yamamoto
- Faculty of Medicine, Department of Orthopaedic Surgery, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan
| | - Noriko Miyake
- Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan
| | - Naomichi Matsumoto
- Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan
| | - Aritoshi Iida
- Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan
| | - Yasuharu Nakashima
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | | | - Yukihide Iwamoto
- Department of Orthopaedic Surgery, Kyushu Rosai Hospital, 1-1 Sonekitamachi, Kokuraminami-ku, Kitakyusyu, 800-0229, Japan
| | - Shiro Ikegawa
- Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan
| |
Collapse
|
|
12
|
Barat-Houari M, Sarrabay G, Gatinois V, Fabre A, Dumont B, Genevieve D, Touitou I. Mutation Update for COL2A1 Gene Variants Associated with Type II Collagenopathies. Hum Mutat 2015; 37:7-15. [PMID: 26443184 DOI: 10.1002/humu.22915] [Citation(s) in RCA: 91] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Accepted: 09/23/2015] [Indexed: 12/19/2022]
Abstract
Mutations in the COL2A1 gene cause a spectrum of rare autosomal-dominant conditions characterized by skeletal dysplasia, short stature, and sensorial defects. An early diagnosis is critical to providing relevant patient care and follow-up, and genetic counseling to affected families. There are no recent exhaustive descriptions of the causal mutations in the literature. Here, we provide a review of COL2A1 mutations extracted from the Leiden Open Variation Database (LOVD) that we updated with data from PubMed and our own patients. Over 700 patients were recorded, harboring 415 different mutations. One-third of the mutations are dominant-negative mutations that affect the glycine residue in the G-X-Y repeats of the alpha 1 chain. These mutations disrupt the collagen triple helix and are common in achondrogenesis type II and hypochondrogenesis. The mutations resulting in a premature stop codon are found in less severe phenotypes such as Stickler syndrome. The p.(Arg275Cys) substitution is found in all patients with COL2A1-associated Czech dysplasia. LOVD-COL2A1 provides support and potential collaborative material for scientific and clinical projects aimed at elucidating phenotype-genotype correlation and differential diagnosis in patients with type II collagenopathies.
Collapse
Affiliation(s)
- Mouna Barat-Houari
- Laboratory of Rare and Autoinflammatory Diseases, CHRU, Montpellier, France.,Genetics & Immunopathology of Inflammatory Osteoarticular Diseases, INSERM UMR1183, Montpellier, France
| | - Guillaume Sarrabay
- Laboratory of Rare and Autoinflammatory Diseases, CHRU, Montpellier, France.,Genetics & Immunopathology of Inflammatory Osteoarticular Diseases, INSERM UMR1183, Montpellier, France
| | - Vincent Gatinois
- Laboratory of Rare and Autoinflammatory Diseases, CHRU, Montpellier, France.,University of Montpellier, Montpellier, France
| | - Aurélie Fabre
- Laboratory of Rare and Autoinflammatory Diseases, CHRU, Montpellier, France
| | - Bruno Dumont
- Laboratory of Rare and Autoinflammatory Diseases, CHRU, Montpellier, France
| | - David Genevieve
- Genetics & Immunopathology of Inflammatory Osteoarticular Diseases, INSERM UMR1183, Montpellier, France.,University of Montpellier, Montpellier, France.,Department of Medical Genetics, Reference Center for Developmental Abnormalities and Constitutional Bone Diseases, CHRU, Montpellier, France
| | - Isabelle Touitou
- Laboratory of Rare and Autoinflammatory Diseases, CHRU, Montpellier, France.,Genetics & Immunopathology of Inflammatory Osteoarticular Diseases, INSERM UMR1183, Montpellier, France.,University of Montpellier, Montpellier, France
| |
Collapse
|