Identification of a novel COL4A5 mutation in a Chinese family with X-linked Alport syndrome using exome sequencing

Alport syndrome (AS) is an inherited disorder and clinically characterized by glomerulonephritis and end-stage kidney disease (ESRD). The aim of this study was to identify the gene responsible for glomerulopathy in a 4-generation Chinese pedigree. Exome sequencing was conducted in four patients of the family, and then direct sequencing was performed in other members of the pedigree. A novel missense mutation c.368G>A (p.Gly123Glu) in the collagen type IV alpha-5 gene (COL4A5) was found to be the genetic cause. The p.Gly123Glu mutation occurs prior to Gly-X-Y repeats in the alpha-5 chain of type IV collagen. Neither sensorineural hearing loss nor ocular abnormalities were present in patients of this family. Other clinical features, such as age of onset, age of ESRD, disease severity and complications, varied among patients of this family. Our finding may provide new insights into the cause and diagnosis of AS, and also have implications for genetic counseling.