1. A novel COL4A5 mutation identified in a Chinese Han family using exome sequencing
- Author
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Fengping Xu, Zhaoyang Zeng, Xiaofei Xiu, Jinzhong Yuan, Xiong Deng, Hongbo Xu, Liping Guan, Sheng Deng, and Jingjing Xiao
- Subjects
Proband ,Adult ,Collagen Type IV ,Male ,China ,Heterozygote ,Article Subject ,DNA Mutational Analysis ,Molecular Sequence Data ,lcsh:Medicine ,Nephritis, Hereditary ,Biology ,medicine.disease_cause ,urologic and male genital diseases ,General Biochemistry, Genetics and Molecular Biology ,Type IV collagen ,Asian People ,medicine ,Ethnicity ,Humans ,Exome ,Family ,Amino Acid Sequence ,Alport syndrome ,Exome sequencing ,Genetics ,Mutation ,General Immunology and Microbiology ,Base Sequence ,lcsh:R ,General Medicine ,medicine.disease ,Pedigree ,Posterior polymorphous corneal dystrophy ,Sensorineural hearing loss ,Female ,Research Article - Abstract
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 collagenα3,α4, andα5 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 theCOL4A5gene 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 typicalCOL4A5-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 theCOL4A5gene associated with AS, which may also shed new light on genetic counseling for AS.
- Published
- 2014