Identification of four novel mutations in the gene identified in Chinese patients with X-linked Alport syndrome.

Alport syndrome (AS) is an inherited progressive nephropathy caused by mutations in one or two of the type IV collagen novel chains (α3, α4 and α5), which are encoded by , and , respectively. To date, three genetic forms of AS have been reported, including X-linked AS, autosomal recessive AS, and autosomal dominant AS, and ~80% of patients have X-linked AS caused by mutations in . In the present study, four novel and one previously reported mutations were identified using targeted next-generation sequencing in Chinese patients suspected of having AS. The results were confirmed by Sanger sequencing, which revealed two novel missense mutations resulting in the substitution of various glycine residues in a collagenous domain containing Gly-X-Y triplet sequence repeats [c.4198G>C, p.(Gly1400Arg) and c.3428G>T, p.(Gly1143Val)], a previously reported missense mutation [c.3071G>A, p.(Gly1024Glu)], a splice site mutation (c.2146+2T>A) and one frameshift mutation [c.1810delC (p.Thr605Ilefs*13)]. After analyzing the affected family members, it was shown that the identified mutations were associated with severe clinical phenotypes. These results broaden the known spectrum of mutations of the gene associated with AS and may have implications for genetic diagnosis, therapy and genetic counseling of affected families.