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BioMed Research International
Volume 2014, Article ID 186048, 5 pages
Research Article

A Novel COL4A5 Mutation Identified in a Chinese Han Family Using Exome Sequencing

1Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
2Department of Pharmacy, Xiangya Hospital, Central South University, Xiangya Road 87, Kaifu District, Changsha, Hunan 410008, China
3Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
4BGI-Shenzhen, Shenzhen, Guangdong 518083, China
5Cancer Research Institute, Xiangya Medical School of Central South University, Changsha, Hunan 410008, China

Received 14 May 2014; Accepted 20 June 2014; Published 6 July 2014

Academic Editor: Yi Guo

Copyright © 2014 Xiaofei Xiu et al. 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.


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.Pro167Gln 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.