Background: Mutations in the COL4A5 gene, encoding the alpha 5 chain of type IV collagen, are responsible for X-linked Alport's syndrome (XLAS), a progressive nephropathy characterized by glomerular basement membrane abnormalities and usually associated with progressive hearing loss and ocular lesions.
Methods: In this study, we analysed all 51 exons of the COL4A5 gene in 20 Chinese patients with XLAS or suspected XLAS from 16 families by using polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE) DNA sequencing.
Results: Five gene mutations identified in five families were considered to be pathogenic, including one nonsense mutation in exon 1 (266C-->T, Gln22Term), two missense mutations in exons 31 (2757G-->T, Gly852Val) and 43 (4142C-->T, Pro1314Ser), and two splice site mutations in introns 1 and 25 just next to the 3' end of their respective exons (283+1G-->T, 2150+1G-->T). According to GenBank, these five mutations have not been reported previously. All male patients have typical clinical manifestations and pathological findings that closely correspond to the effects of the mutations. Furthermore, seven gene polymorphisms were detected in introns 18 and 10 and exons 20, 27, 29, 39 and 46. Only the substitution in intron 18 (1234+25G-->A) had a gene frequency significantly higher in patients than in normal individuals.
Conclusion: Our study demonstrated the critical role of COL4A5 gene mutations in the pathogenesis of XLAS. The linkage of the polymorphism to AS is still unknown.