Background: The clinical and pathological features of Alport syndrome are characterized by abnormalities in the basement membrane collagen network which are composed of the α3, α4 and α5 chains of type IV collagen and usually associated with hearing loss and ocular lesions. The predominant form (85% of AS) is inherited as X-linked mode (XLAS) caused by mutations encoding the α5 chain of type IV collagen gene, COL4A5. Different mutations in the COL4A5 gene have been reported widely, but only a few mutations were identified in Chinese patients.
Methods: We studied 71 Chinese patients from 35 unrelated families with XLAS confirmed by skin biopsy. Genomic DNA was extracted from peripheral blood of all patients. All 51 exons of the COL4A5 gene were screened by direct sequencing for the probands.
Results: A total of twenty-five identified gene mutations were considered to be pathogenic, including 1 nonsense, 1 splice-site, 1 complex rearrangement, 5 small deletions, 2 small insertions and 15 missense mutations. Twenty-one mutations have not been reported previously.
Conclusions: We have identified 25 pathogenic mutations in 35 Chinese families with XLAS. Skin biopsy is effective for the diagnosis of XLAS.