title: Identification of a novel collagen type IV alpha-4 (COL4A4) mutation in a Chinese family with autosomal dominant Alport syndrome using exome sequencing.
abstract: OBJECTIVE
  Alport syndrome (AS) is an inherited disorder characterized by glomerulonephritis and end-stage renal disease (ESRD). The aim of this study was to identify the gene responsible for the glomerulopathy in a Chinese family with autosomal dominant AS using exome sequencing.
  
  
  METHODS
  A 4-generation, 30-member Chinese Han family was enrolled in this study. Exome sequencing was conducted in the proband of the family, and then direct sequencing was performed in family members of the pedigree and 100 normal controls.
  
  
  RESULTS
  A novel frameshift mutation, c.3213delA (p.Gly1072GlufsFNx0169), in the collagen type IV alpha-4 gene (COL4A4) was found to be the genetic cause. Neither sensorineural hearing loss nor ocular abnormalities were present in the patients of this family. Other clinical features, such as age of onset, age of ESRD occurring and disease severity, varied among the patients of this family.
  
  
  CONCLUSIONS
  A novel frameshift mutation, c.3213delA (p.Gly1072GlufsFNx0169) in the COL4A4 gene, was identified in the Chinese pedigree with autosomal dominant AS. Our findings may provide new insights into the cause and diagnosis of AS and also have implications for genetic counselling.
authors.affiliation: Center for Experimental Medicine & Department of Neurology, The Third Xiangya Hospital; Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, PR China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Deng
authors.affiliation: Center for Experimental Medicine & Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, PR China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, PR China.
authors.forename: Jinzhong
authors.initials: J
authors.lastname: Yuan
authors.affiliation: BGI-Shenzhen, Shenzhen, PR China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Center for Experimental Medicine & Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, PR China.
authors.forename: Lamei
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Center for Experimental Medicine & Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, PR China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Deng
authors.affiliation: BGI-Shenzhen, Shenzhen, PR China.
authors.forename: Liping
authors.initials: L
authors.lastname: Guan
authors.affiliation: Center for Experimental Medicine & Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, PR China.
authors.forename: Anding
authors.initials: A
authors.lastname: Zhu
authors.affiliation: Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, PR China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Rong
authors.affiliation: BGI-Shenzhen, Shenzhen, PR China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Center for Experimental Medicine & Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Deng
mesh_terms: D000328:Adult; D044466:Asian People; D024141:Collagen Type IV / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009394:Nephritis, Hereditary / Q000235:genetics* / Q000473:pathology; D010375:Pedigree
chemical_list: D024141:Collagen Type IV