A start codon mutation of the TSPAN12 gene in Chinese families causes clinical heterogeneous familial exudative vitreoretinopathy
Abstract Background Familial exudative vitreoretinopathy (FEVR) is a severe clinically and genetically heterogeneous retinal disorder characterized with failure of vascular development of the peripheral retina. The symptoms of FEVR vary widely among patients in the same family, and even between the...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-10-01
|
| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.948 |
| _version_ | 1797301063641989120 |
|---|---|
| author | Wei Li Ziwei Wang Yan Sun Zhuoshi Wang Jinyue Bai Bo Xing Xiao Sun Lusheng Wang Jiankang Li Wei He |
| author_facet | Wei Li Ziwei Wang Yan Sun Zhuoshi Wang Jinyue Bai Bo Xing Xiao Sun Lusheng Wang Jiankang Li Wei He |
| author_sort | Wei Li |
| collection | DOAJ |
| description | Abstract Background Familial exudative vitreoretinopathy (FEVR) is a severe clinically and genetically heterogeneous retinal disorder characterized with failure of vascular development of the peripheral retina. The symptoms of FEVR vary widely among patients in the same family, and even between the two eyes of a given patient. The purpose of this study was to investigate the molecular mechanisms by which the start codon mutation of the TSPAN12 causes difference in clinical manifestations between individuals in the same family. Methods Next‐generation sequencing (NGS)‐based target capture sequencing was performed in proband with a diagnosis of FEVR and their normal visual acuity family members. Cosegregation analysis of the candidate causative variant was performed in additional family members by using Sanger sequencing. Complete fundus examination, fundus fluorescein angiography (FFA), and family history collection were performed in all family members. Potential candidate causative variants were verified with reference to guidelines and standards from the American College of Medical Genetics and Genomics. Results We identified a novel heterozygous missense mutation (c.1A>G, p.M1V) localized in the start codon of the TSPAN12 and was detected as a potentially disease‐causing variant for the proband. Retrospective analysis of clinical data, fundus examination, and FFA showed that the mutant carrier presented peripheral retinal vascular anomalies in early stages, and visual acuity did not show significant effects. However, the proband who carried this mutation and his cousin showed typical high‐stage FEVR fundus changes coupled with a sharp decline in vision. Conclusions We report a novel start codon mutation (c.1A>G, p.M1V) in the TSPAN12 that causes clinically heterogeneous manifestations. Our results expand the mutation spectrums of TSPAN12, and will be valuable for disease diagnosis, prognosis, genetic counseling, and enriching our understanding of the role of the tetraspanin‐12 protein in the pathogenesis of FEVR. |
| first_indexed | 2024-03-07T23:17:00Z |
| format | Article |
| id | doaj.art-768d212a70674c608802e4a06f6ee6ed |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T23:17:00Z |
| publishDate | 2019-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-768d212a70674c608802e4a06f6ee6ed2024-02-21T10:29:27ZengWileyMolecular Genetics & Genomic Medicine2324-92692019-10-01710n/an/a10.1002/mgg3.948A start codon mutation of the TSPAN12 gene in Chinese families causes clinical heterogeneous familial exudative vitreoretinopathyWei Li0Ziwei Wang1Yan Sun2Zhuoshi Wang3Jinyue Bai4Bo Xing5Xiao Sun6Lusheng Wang7Jiankang Li8Wei He9BGI Education Center University of Chinese Academy of Sciences Shenzhen ChinaBGI Education Center University of Chinese Academy of Sciences Shenzhen ChinaHe's university Shenyang ChinaHe's university Shenyang ChinaSchool of Basic Medicine Qingdao University Qingdao ChinaSchool of Basic Medicine Qingdao University Qingdao ChinaSchool of Basic Medicine Qingdao University Qingdao ChinaHe's university Shenyang ChinaHe's university Shenyang ChinaHe's university Shenyang ChinaAbstract Background Familial exudative vitreoretinopathy (FEVR) is a severe clinically and genetically heterogeneous retinal disorder characterized with failure of vascular development of the peripheral retina. The symptoms of FEVR vary widely among patients in the same family, and even between the two eyes of a given patient. The purpose of this study was to investigate the molecular mechanisms by which the start codon mutation of the TSPAN12 causes difference in clinical manifestations between individuals in the same family. Methods Next‐generation sequencing (NGS)‐based target capture sequencing was performed in proband with a diagnosis of FEVR and their normal visual acuity family members. Cosegregation analysis of the candidate causative variant was performed in additional family members by using Sanger sequencing. Complete fundus examination, fundus fluorescein angiography (FFA), and family history collection were performed in all family members. Potential candidate causative variants were verified with reference to guidelines and standards from the American College of Medical Genetics and Genomics. Results We identified a novel heterozygous missense mutation (c.1A>G, p.M1V) localized in the start codon of the TSPAN12 and was detected as a potentially disease‐causing variant for the proband. Retrospective analysis of clinical data, fundus examination, and FFA showed that the mutant carrier presented peripheral retinal vascular anomalies in early stages, and visual acuity did not show significant effects. However, the proband who carried this mutation and his cousin showed typical high‐stage FEVR fundus changes coupled with a sharp decline in vision. Conclusions We report a novel start codon mutation (c.1A>G, p.M1V) in the TSPAN12 that causes clinically heterogeneous manifestations. Our results expand the mutation spectrums of TSPAN12, and will be valuable for disease diagnosis, prognosis, genetic counseling, and enriching our understanding of the role of the tetraspanin‐12 protein in the pathogenesis of FEVR.https://doi.org/10.1002/mgg3.948clinical heterogeneous manifestationsFamilial exudative vitreoretinopathyfundus fluorescein angiographystart codon mutation |
| spellingShingle | Wei Li Ziwei Wang Yan Sun Zhuoshi Wang Jinyue Bai Bo Xing Xiao Sun Lusheng Wang Jiankang Li Wei He A start codon mutation of the TSPAN12 gene in Chinese families causes clinical heterogeneous familial exudative vitreoretinopathy Molecular Genetics & Genomic Medicine clinical heterogeneous manifestations Familial exudative vitreoretinopathy fundus fluorescein angiography start codon mutation |
| title | A start codon mutation of the TSPAN12 gene in Chinese families causes clinical heterogeneous familial exudative vitreoretinopathy |
| title_full | A start codon mutation of the TSPAN12 gene in Chinese families causes clinical heterogeneous familial exudative vitreoretinopathy |
| title_fullStr | A start codon mutation of the TSPAN12 gene in Chinese families causes clinical heterogeneous familial exudative vitreoretinopathy |
| title_full_unstemmed | A start codon mutation of the TSPAN12 gene in Chinese families causes clinical heterogeneous familial exudative vitreoretinopathy |
| title_short | A start codon mutation of the TSPAN12 gene in Chinese families causes clinical heterogeneous familial exudative vitreoretinopathy |
| title_sort | start codon mutation of the tspan12 gene in chinese families causes clinical heterogeneous familial exudative vitreoretinopathy |
| topic | clinical heterogeneous manifestations Familial exudative vitreoretinopathy fundus fluorescein angiography start codon mutation |
| url | https://doi.org/10.1002/mgg3.948 |
| work_keys_str_mv | AT weili astartcodonmutationofthetspan12geneinchinesefamiliescausesclinicalheterogeneousfamilialexudativevitreoretinopathy AT ziweiwang astartcodonmutationofthetspan12geneinchinesefamiliescausesclinicalheterogeneousfamilialexudativevitreoretinopathy AT yansun astartcodonmutationofthetspan12geneinchinesefamiliescausesclinicalheterogeneousfamilialexudativevitreoretinopathy AT zhuoshiwang astartcodonmutationofthetspan12geneinchinesefamiliescausesclinicalheterogeneousfamilialexudativevitreoretinopathy AT jinyuebai astartcodonmutationofthetspan12geneinchinesefamiliescausesclinicalheterogeneousfamilialexudativevitreoretinopathy AT boxing astartcodonmutationofthetspan12geneinchinesefamiliescausesclinicalheterogeneousfamilialexudativevitreoretinopathy AT xiaosun astartcodonmutationofthetspan12geneinchinesefamiliescausesclinicalheterogeneousfamilialexudativevitreoretinopathy AT lushengwang astartcodonmutationofthetspan12geneinchinesefamiliescausesclinicalheterogeneousfamilialexudativevitreoretinopathy AT jiankangli astartcodonmutationofthetspan12geneinchinesefamiliescausesclinicalheterogeneousfamilialexudativevitreoretinopathy AT weihe astartcodonmutationofthetspan12geneinchinesefamiliescausesclinicalheterogeneousfamilialexudativevitreoretinopathy AT weili startcodonmutationofthetspan12geneinchinesefamiliescausesclinicalheterogeneousfamilialexudativevitreoretinopathy AT ziweiwang startcodonmutationofthetspan12geneinchinesefamiliescausesclinicalheterogeneousfamilialexudativevitreoretinopathy AT yansun startcodonmutationofthetspan12geneinchinesefamiliescausesclinicalheterogeneousfamilialexudativevitreoretinopathy AT zhuoshiwang startcodonmutationofthetspan12geneinchinesefamiliescausesclinicalheterogeneousfamilialexudativevitreoretinopathy AT jinyuebai startcodonmutationofthetspan12geneinchinesefamiliescausesclinicalheterogeneousfamilialexudativevitreoretinopathy AT boxing startcodonmutationofthetspan12geneinchinesefamiliescausesclinicalheterogeneousfamilialexudativevitreoretinopathy AT xiaosun startcodonmutationofthetspan12geneinchinesefamiliescausesclinicalheterogeneousfamilialexudativevitreoretinopathy AT lushengwang startcodonmutationofthetspan12geneinchinesefamiliescausesclinicalheterogeneousfamilialexudativevitreoretinopathy AT jiankangli startcodonmutationofthetspan12geneinchinesefamiliescausesclinicalheterogeneousfamilialexudativevitreoretinopathy AT weihe startcodonmutationofthetspan12geneinchinesefamiliescausesclinicalheterogeneousfamilialexudativevitreoretinopathy |