Identification of a novel pathogenic COL4A3 gene mutation in a Chinese family with autosomal dominant Alport syndrome: A case report

Alport syndrome (AS) is a genetic disease with various manifestations, including hematuria, proteinuria, impaired renal function and potential ocular or auditory abnormalities. Mutations in the collagen type IV alpha 3 chain (COL4A3), collagen type IV alpha 4 chain and collagen type IV alpha 5 chain genes encoding the alpha 3, alpha 4 and alpha 5 chains of type IV collagen may undermine glomerular basement membrane (GBM) integrity and cause persistent renal deterioration. In the present study, the case of a Chinese family diagnosed with AS was examined. Pedigree investigations and whole exome sequencing (WES) revealed the presence of two heterozygous mutations (c.2603G>A; p.G868E, and c.583G>A; p.G195S) in the COL4A3 gene. p.G868E was identified as the 'culprit' mutation, whereas p.G195S was identified as an 'auxiliary' mutation for AS with regards to the manifestations observed in the patients carrying each of the gene mutations. In conclusion, these findings suggested that c.2603G>A may be a novel overt pathogenic mutation site for autosomal dominant AS. In addition, WES may be effective for the early diagnosis and medical intervention of AS, and may be widely used for AS prognosis prediction and pre-implantation genetic diagnosis.