rs104886202

This study describes a novel multiplex genomic PCR-SSCP method for detecting COL4A5 mutations causing X-linked Alport syndrome. Applied to 46 US families, the method identified 31 mutations (detection sensitivity >79%), including 3 multi-exon deletions, 26 single-base mutations, and 10 polymorphisms. Notable findings include: (1) discovery that the 2948 A→G mutation causes exon 32 skipping rather than the expected missense change S916G; (2) identification of M898V as a possibly pathogenic missense variant with an unusually mild phenotype; (3) characterization of L1649R as a common founder mutation in the US population.

This paper describes an efficient multiplex PCR-SSCP method for screening COL4A5 mutations in Alport syndrome patients. Application to 46 U.S. families identified 29 distinct mutations (deletions, frameshifts, splice site alterations, and missense changes) with detection sensitivity >79%, including novel findings such as exon 32 skipping caused by an internal exon mutation (2948A→G) and identification of Met898Val associated with mild disease phenotype.