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A Novel COL4A5 Mutation Identified in a Chinese Han Family Using Exome Sequencing
Alport syndrome (AS) is a monogenic disease of the basement membrane (BM), resulting in progressive renal failure due to glomerulonephropathy, variable sensorineural hearing loss, and ocular anomalies. It is caused by mutations in the collagen type IV alpha-3 gene (COL4A3), the collagen type IV alph...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Hindawi Publishing Corporation
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4109303/ https://www.ncbi.nlm.nih.gov/pubmed/25110662 http://dx.doi.org/10.1155/2014/186048 |
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author | Xiu, Xiaofei Yuan, Jinzhong Deng, Xiong Xiao, Jingjing Xu, Hongbo Zeng, Zhaoyang Guan, Liping Xu, Fengping Deng, Sheng |
author_facet | Xiu, Xiaofei Yuan, Jinzhong Deng, Xiong Xiao, Jingjing Xu, Hongbo Zeng, Zhaoyang Guan, Liping Xu, Fengping Deng, Sheng |
author_sort | Xiu, Xiaofei |
collection | PubMed |
description | Alport syndrome (AS) is a monogenic disease of the basement membrane (BM), resulting in progressive renal failure due to glomerulonephropathy, variable sensorineural hearing loss, and ocular anomalies. It is caused by mutations in the collagen type IV alpha-3 gene (COL4A3), the collagen type IV alpha-4 gene (COL4A4), and the collagen type IV alpha-5 gene (COL4A5), which encodes type IV collagen α3, α4, and α5 chains, respectively. To explore the disease-related gene in a four-generation Chinese Han pedigree of AS, exome sequencing was conducted on the proband, and a novel deletion mutation c.499delC (p.Pro167Glnfs*36) in the COL4A5 gene was identified. This mutation, absent in 1,000 genomes project, HapMap, dbSNP132, YH1 databases, and 100 normal controls, cosegregated with patients in the family. Neither sensorineural hearing loss nor typical COL4A5-related ocular abnormalities (dot-and-fleck retinopathy, anterior lenticonus, and the rare posterior polymorphous corneal dystrophy) were present in patients of this family. The phenotypes of patients in this AS family were characterized by early onset-age and rapidly developing into end-stage renal disease (ESRD). Our discovery broadens the mutation spectrum in the COL4A5 gene associated with AS, which may also shed new light on genetic counseling for AS. |
format | Online Article Text |
id | pubmed-4109303 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-41093032014-08-10 A Novel COL4A5 Mutation Identified in a Chinese Han Family Using Exome Sequencing Xiu, Xiaofei Yuan, Jinzhong Deng, Xiong Xiao, Jingjing Xu, Hongbo Zeng, Zhaoyang Guan, Liping Xu, Fengping Deng, Sheng Biomed Res Int Research Article Alport syndrome (AS) is a monogenic disease of the basement membrane (BM), resulting in progressive renal failure due to glomerulonephropathy, variable sensorineural hearing loss, and ocular anomalies. It is caused by mutations in the collagen type IV alpha-3 gene (COL4A3), the collagen type IV alpha-4 gene (COL4A4), and the collagen type IV alpha-5 gene (COL4A5), which encodes type IV collagen α3, α4, and α5 chains, respectively. To explore the disease-related gene in a four-generation Chinese Han pedigree of AS, exome sequencing was conducted on the proband, and a novel deletion mutation c.499delC (p.Pro167Glnfs*36) in the COL4A5 gene was identified. This mutation, absent in 1,000 genomes project, HapMap, dbSNP132, YH1 databases, and 100 normal controls, cosegregated with patients in the family. Neither sensorineural hearing loss nor typical COL4A5-related ocular abnormalities (dot-and-fleck retinopathy, anterior lenticonus, and the rare posterior polymorphous corneal dystrophy) were present in patients of this family. The phenotypes of patients in this AS family were characterized by early onset-age and rapidly developing into end-stage renal disease (ESRD). Our discovery broadens the mutation spectrum in the COL4A5 gene associated with AS, which may also shed new light on genetic counseling for AS. Hindawi Publishing Corporation 2014 2014-07-06 /pmc/articles/PMC4109303/ /pubmed/25110662 http://dx.doi.org/10.1155/2014/186048 Text en Copyright © 2014 Xiaofei Xiu et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Xiu, Xiaofei Yuan, Jinzhong Deng, Xiong Xiao, Jingjing Xu, Hongbo Zeng, Zhaoyang Guan, Liping Xu, Fengping Deng, Sheng A Novel COL4A5 Mutation Identified in a Chinese Han Family Using Exome Sequencing |
title | A Novel COL4A5 Mutation Identified in a Chinese Han Family Using Exome Sequencing |
title_full | A Novel COL4A5 Mutation Identified in a Chinese Han Family Using Exome Sequencing |
title_fullStr | A Novel COL4A5 Mutation Identified in a Chinese Han Family Using Exome Sequencing |
title_full_unstemmed | A Novel COL4A5 Mutation Identified in a Chinese Han Family Using Exome Sequencing |
title_short | A Novel COL4A5 Mutation Identified in a Chinese Han Family Using Exome Sequencing |
title_sort | novel col4a5 mutation identified in a chinese han family using exome sequencing |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4109303/ https://www.ncbi.nlm.nih.gov/pubmed/25110662 http://dx.doi.org/10.1155/2014/186048 |
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