Genotype–phenotype correlations in 17 Chinese patients with autosomal recessive Alport syndrome

Autosomal recessive Alport syndrome (ARAS) results from mutations in the COL4A3 or COL4A4 gene. We analyzed the genotype and phenotype of 17 unrelated Chinese patients with ARAS. Clinical data were reviewed. All coding exons of COL4A3 and COL4A4 genes were PCR-amplified and sequenced from genomic DNA. We identified pathologic mutations in all patients, giving a mutation detection rate of 100%, with 82% in COL4A3 gene and 18% in COL4A4 gene. Sixteen novel mutations in COL4A3 gene and four novel mutations in COL4A4 gene were identified. Furthermore, a previously reported in-frame deletion mutation (40_63del24) in exon 1 of the COL4A3 gene was found in four patients in our study. A single 40_63del24 mutation in COL4A3 seems to result in mild or no renal manifestations, whereas the homozygous state of 40_63del24 in COL4A3 gene or compound heterozygous mutation of 40_63del24 plus another nonsense or frameshift mutation in COL4A3 gene seems to result severe ARAS with hearing loss. Half of the probands' parents had hematuria with or without mild proteinuria. Therefore, we recommend that ARAS be considered when a patient has a positive family history of hematuria, and screening for COL4A3 mutations firstly may be an efficient strategy for molecular diagnosis of ARAS.