摘要：Alport syndrome (ATS) is an inherited glomerular disease caused by mutations in one of the type IV collagen novel chains (α3, α4, and α5). ATS is characterized by persistent microscopic hematuria starting from infancy, eventually leading to either progressive nephritis or end-stage renal disease. There are three known genetic forms of ATS, i.e., X-linked ATS, autosomal recessive ATS, and autosomal dominant ATS. About 80% of patients with ATS have X-linked ATS, caused by mutations in the type IV collagen α5 chain gene, COL4A5. Mutation detection rates are about 80% in males with X-linked ATS, however, there are some difficulties in the genetic diagnosis of ATS. Most mutations are point mutations without hot spots in the COL4A3, COL4A4, and COL4A5 genes. Further, there is insufficient data on COL4A3 and COL4A4 mutation detection for the mutations to be compared between patients with either autosomal recessive or dominant ATS. Therefore, diagnosis can be a challenge from a clinical perspective in female patients with ATS with no apparent family history. Therefore, in this study, we used whole-exome sequencing (WES) to identify mutations in type IV collagen in two girls with suspicious glomerular basement membrane structural changes associated with ATS, but no relevant family history. Our results revealed de novo c.4688G>A (p.Arg1563Gln) and c.2714G>A (p.Gly905Asp) mutations in COL4A5. We therefore suggest that WES is an effective approach to obtain genetic information in ATS, particularly in female patients without a relevant family history, to detect unexpected DNA variations.
关键词：Alport Syndrome;Child;Collagen Type IV;Whole Exome Sequencing
