title: A novel COL4A5 mutation identified in a Chinese Han family using exome sequencing.
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 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.
authors.affiliation: Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China ; Department of Pharmacy, Xiangya Hospital, Central South University, Xiangya Road 87, Kaifu District, Changsha, Hunan 410008, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Xiu
authors.affiliation: Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
authors.forename: Jinzhong
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Deng
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong 518083, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Xu
authors.affiliation: Cancer Research Institute, Xiangya Medical School of Central South University, Changsha, Hunan 410008, China.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong 518083, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Guan
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong 518083, China.
authors.forename: Fengping
authors.initials: F
authors.lastname: Xu
authors.affiliation: Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China ; Department of Pharmacy, Xiangya Hospital, Central South University, Xiangya Road 87, Kaifu District, Changsha, Hunan 410008, China.
authors.forename: Sheng
authors.identifier: 0000-0002-8313-6522
authors.initials: S
authors.lastname: Deng
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002681:China; D024141:Collagen Type IV / Q000737:chemistry / Q000235:genetics*; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics*; D059472:Exome / Q000235:genetics*; D005190:Family; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009394:Nephritis, Hereditary / Q000235:genetics; D010375:Pedigree
chemical_list: C478159:COL4A5 protein, human; D024141:Collagen Type IV
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