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Molecular Genetics of the COL2A1-Related Disorders

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Molecular Genetics of the COL2A1-Related Disorders Mutation Research 768 (2016) 1–13 Contents lists available at ScienceDirect Mutation Research/Reviews in Mutation Research journal homepage: www.elsevier.com/locate/reviewsmr Communit y address: www.elsevier.com/locate/mutres Review Molecular genetics of the COL2A1-related disorders ,1 1 Hao Deng* , Xiangjun Huang , Lamei Yuan Center for Experimental Medicine and Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha 410013, China A R T I C L E I N F O A B S T R A C T Article history: Type II collagen, comprised of three identical alpha-1(II) chains, is the major collagen synthesized by Received 19 June 2015 chondrocytes, and is found in articular cartilage, vitreous humour, inner ear and nucleus pulposus. Received in revised form 8 January 2016 Mutations in the collagen type II alpha-1 gene (COL2A1) have been reported to be responsible for a series Accepted 23 February 2016 of abnormalities, known as type II collagenopathies. To date, 16 definite disorders, inherited in an Available online 2 March 2016 autosomal dominant or recessive pattern, have been described to be associated with the COL2A1 mutations, and at least 405 mutations ranging from point mutations to complex rearrangements have Keywords: been reported, though the underlying pathogenesis remains unclear. Significant clinical heterogeneity The COL2A1 gene has been reported in COL2A1-associated type II collagenopathies. In this review, we highlight current Type II collagenopathies knowledge of known mutations in the COL2A1 gene for these disorders, as well as genetic animal models Gene mutation Genetics related to the COL2A1 gene, which may help us understand the nature of complex phenotypes and Heterogeneity underlying pathogenesis of these conditions. ã 2016 Elsevier B.V. All rights reserved. Contents 1. Introduction . 2 1.1. The COL2A1 gene and its protein . 3 2. Genetic disorders and COL2A1 mutations . 3 2.1. Achondrogenesis type II or hypochondrogenesis (ACG2 or HCG) . 4 2.2. Platyspondylic skeletal dysplasia, Torrance type and spondyloperipheral dysplasia (PLSDT and SPD) . 4 2.3. Spondyloepiphyseal dysplasia congenita (SEDC) . 5 2.4. Spondyloepimetaphyseal dysplasia, Strudwick type (SEMDSTWK) . 5 2.5. Kniest dysplasia . 5 2.6. Stickler syndrome type I (STL1) and nonsyndromic ocular STL1 . 5 2.7. Osteoarthritis with mild chondrodysplasia . 6 2.8. Avascular necrosis of the femoral head (ANFH) . 6 2.9. Legg–Calve–Perthes disease (LCPD) . 7 2.10. Epiphyseal dysplasia, multiple with myopia and deafness (EDMMD) . 7 2.11. Otospondylomegaepiphyseal dysplasia (OSMED) . 7 2.12. Czech dysplasia . 7 2.13. Spondyloepiphyseal dysplasia, Namaqualand type (SEDN) . 7 2.14. Vitreoretinopathy with phalangeal epiphyseal dysplasia (VPED) . 8 2.15. Mutations described in the COL2A1 gene with other conditions . 8 3. The COL2A1-related animal models . 8 Abbreviations: COL2A1, the collagen type II alpha-1 gene; OMIM, Online Mendelian Inheritance in Man; ACG2/HCG, achondrogenesis type II/hypochondrogenesis; PLSDT, platyspondylic skeletal dysplasia, Torrance type; SPD, spondyloperipheral dysplasia; SEDC, spondyloepiphyseal dysplasia congenita; SEMDSTWK, spondyloepimetaphyseal dysplasia, Strudwick type; STL1, Stickler syndrome type I; DRRD, dominantly inherited rhegmatogenous retinal detachment; ANFH, avascular necrosis of the femoral head; LCPD, Legg–Calve–Perthes disease; EDMMD, epiphyseal dysplasia, multiple with myopia and deafness; OSMED, otospondylomegaepiphyseal dysplasia; SEDN, spondyloepiphyseal dysplasia, Namaqualand type; VPED, vitreoretinopathy with phalangeal epiphyseal dysplasia; HGMD, human gene mutation database; indel, insertion–deletion; DSC, dysspondyloenchondromatosis; Dmm, disproportionate micromelia; ENU, N-ethyl-N-nitrosourea. * Corresponding author at: The Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha, Hunan 410013, China. Fax: +86 731 88618339. E-mail address: [email protected] (H. Deng). 1 These authors have contributed equally to the work. http://dx.doi.org/10.1016/j.mrrev.2016.02.003 1383-5742/ã 2016 Elsevier B.V. All rights reserved. 2 H. Deng et al. / Mutation Research 768 (2016) 1–13 4. Conclusions . 8 Conflict of interest . 9 Acknowledgements . 9 References . 9 1. Introduction otospondylomegaepiphyseal dysplasia (OSMED, OMIM 215150), Czech dysplasia (OMIM 609162), spondyloepiphyseal dysplasia, Type II collagen, comprised of three identical alpha-1(II) Namaqualand type (SEDN), and vitreoretinopathy with phalangeal chains, is the major collagen synthesized by chondrocytes, epiphyseal dysplasia (VPED) (Fig. 1). These disorders are clinically distributing in articular cartilage, vitreous humour, inner ear characterized by different serious abnormalities in the ocular, and nucleus pulposus [1]. Mutations in the collagen type II alpha- skeletal, oro-facial, and audiological systems (Table 1). Clinical 1 gene (COL2A1, OMIM 120140) have been described to be variability and phenotypic overlap in COL2A1-related disorders responsible for a series of abnormalities, known as type II were commonly observed in patients, even within the same family collagenopathies. Significant progresses in mutation analysis of [5]. Though the prevalence as a whole is unknown, the worldwide the COL2A1 gene and type II collagenopathies have been achieved estimated incidence is more than 20.4–35.9/100,000 in different in the last twenty-six years [2–4]. The COL2A1 mutations were regions and populations [6–10]. reported to be responsible for at least 16 definite disorders, For this review, we searched literatures in NCBI PubMed including achondrogenesis type II/hypochondrogenesis (ACG2/ database using the search terms “COL2A1”, “collagen type II alpha- HCG, OMIM 200610), platyspondylic skeletal dysplasia, Torrance 1”, “epiphyseal dysplasia”, “skeletal dysplasia”, “spondyloepiphy- type (PLSDT, OMIM 151210), spondyloperipheral dysplasia (SPD, seal dysplasia”, and “multiple epiphyseal dysplasia”, in combina- OMIM 271700), spondyloepiphyseal dysplasia congenita (SEDC, tion with “genetics”, “mutation”, and “variant” from January OMIM 183900), spondyloepimetaphyseal dysplasia, Strudwick 1980 to June 2015, and other related papers were also retrieved type (SEMDSTWK, OMIM 184250), Kniest dysplasia (OMIM from important papers using reference lists. Only those publica- 156550), Stickler syndrome type I (STL1, OMIM 108300), non- tions in English were included. In this review, we provide an syndromic ocular STL1 (OMIM 609508), osteoarthritis with mild overview of the COL2A1 gene and its protein, COL2A1-related chondrodysplasia (OMIM 604864), avascular necrosis of the disorders and clinical features, genotype-phenotype associations, femoral head (ANFH, OMIM 608805), Legg–Calve–Perthes disease and related animal models, which may provide us better (LCPD, OMIM 150600), epiphyseal dysplasia, multiple with myopia understanding of the pathogenesis, and contribute to clinical and deafness (EDMMD, OMIM 132450), diagnosis and therapeutic strategies. Fig. 1. The phenotypic spectrum of type II collagenopathies. Symbols indicate clinical manifestations, and overlapping portions between disorders indicate shared phenotypes. ACG2, achondrogenesis type II; HCG, hypochondrogenesis; PLSDT, platyspondylic skeletal dysplasia, Torrance type; SPD, spondyloperipheral dysplasia; SEDC, spondyloepiphyseal dysplasia congenita; SEMDSTWK, spondyloepimetaphyseal dysplasia, Strudwick type; STL1, Stickler syndrome type I; OA, osteoarthritis; ANFH, avascular necrosis of the femoral head; LCPD, Legg-Calve-Perthes disease; EDMMD, epiphyseal dysplasia, multiple with myopia and deafness; OSMED, otospondylomegaepiphyseal dysplasia; SEDN, spondyloepiphyseal dysplasia, Namaqualand type; VPED, vitreoretinopathy with phalangeal epiphyseal dysplasia. Download English Version: https://daneshyari.com/en/article/2149550 Download Persian Version: https://daneshyari.com/article/2149550 Daneshyari.com.
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