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Identification of a New Mutation p.P88L in Connexin 50 Associated with Dominant Congenital Cataract
Congenital hereditary cataract is genetically heterogeneous and the leading cause of visual impairment in children. Identification of hereditary causes is critical to genetic counselling and family planning. Here, we examined a four-generation Chinese pedigree with congenital dominant cataract and i...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068895/ https://www.ncbi.nlm.nih.gov/pubmed/35531093 http://dx.doi.org/10.3389/fcell.2022.794837 |
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author | Jin, Aixia Zhao, Qingqing Liu, Shuting Jin, Zi-bing Li, Shuyan Xiang, Mengqing Zeng, Mingbing Jin, Kangxin |
author_facet | Jin, Aixia Zhao, Qingqing Liu, Shuting Jin, Zi-bing Li, Shuyan Xiang, Mengqing Zeng, Mingbing Jin, Kangxin |
author_sort | Jin, Aixia |
collection | PubMed |
description | Congenital hereditary cataract is genetically heterogeneous and the leading cause of visual impairment in children. Identification of hereditary causes is critical to genetic counselling and family planning. Here, we examined a four-generation Chinese pedigree with congenital dominant cataract and identified a new mutation in GJA8 via targeted exome sequencing. A heterozygous missense mutation c.263C > T, leading to a proline-to-Leucine conversion at the conserved residue 88 in the second transmembrane domain of human connexin 50 (Cx50), was identified in all patients but not in unaffected family members. Functional analyses of the mutation revealed that it disrupted the stability of Cx50 and had a deleterious effect on protein function. Indeed, the mutation compromised normal membrane permeability and gating of ions, and impeded cell migration when overexpressed. Together, our results expand the pathogenic mutation spectrum of Cx50 underlying congenital cataract and lend more support to clinical diagnosis and genetic counseling. |
format | Online Article Text |
id | pubmed-9068895 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90688952022-05-05 Identification of a New Mutation p.P88L in Connexin 50 Associated with Dominant Congenital Cataract Jin, Aixia Zhao, Qingqing Liu, Shuting Jin, Zi-bing Li, Shuyan Xiang, Mengqing Zeng, Mingbing Jin, Kangxin Front Cell Dev Biol Cell and Developmental Biology Congenital hereditary cataract is genetically heterogeneous and the leading cause of visual impairment in children. Identification of hereditary causes is critical to genetic counselling and family planning. Here, we examined a four-generation Chinese pedigree with congenital dominant cataract and identified a new mutation in GJA8 via targeted exome sequencing. A heterozygous missense mutation c.263C > T, leading to a proline-to-Leucine conversion at the conserved residue 88 in the second transmembrane domain of human connexin 50 (Cx50), was identified in all patients but not in unaffected family members. Functional analyses of the mutation revealed that it disrupted the stability of Cx50 and had a deleterious effect on protein function. Indeed, the mutation compromised normal membrane permeability and gating of ions, and impeded cell migration when overexpressed. Together, our results expand the pathogenic mutation spectrum of Cx50 underlying congenital cataract and lend more support to clinical diagnosis and genetic counseling. Frontiers Media S.A. 2022-04-21 /pmc/articles/PMC9068895/ /pubmed/35531093 http://dx.doi.org/10.3389/fcell.2022.794837 Text en Copyright © 2022 Jin, Zhao, Liu, Jin, Li, Xiang, Zeng and Jin. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Jin, Aixia Zhao, Qingqing Liu, Shuting Jin, Zi-bing Li, Shuyan Xiang, Mengqing Zeng, Mingbing Jin, Kangxin Identification of a New Mutation p.P88L in Connexin 50 Associated with Dominant Congenital Cataract |
title | Identification of a New Mutation p.P88L in Connexin 50 Associated with Dominant Congenital Cataract |
title_full | Identification of a New Mutation p.P88L in Connexin 50 Associated with Dominant Congenital Cataract |
title_fullStr | Identification of a New Mutation p.P88L in Connexin 50 Associated with Dominant Congenital Cataract |
title_full_unstemmed | Identification of a New Mutation p.P88L in Connexin 50 Associated with Dominant Congenital Cataract |
title_short | Identification of a New Mutation p.P88L in Connexin 50 Associated with Dominant Congenital Cataract |
title_sort | identification of a new mutation p.p88l in connexin 50 associated with dominant congenital cataract |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068895/ https://www.ncbi.nlm.nih.gov/pubmed/35531093 http://dx.doi.org/10.3389/fcell.2022.794837 |
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