Linkage analysis and a novel COL4A5 mutation in a large Turkish family with Alport syndrome

Alport syndrome (AS) is a renal disease that is characterized by proteinuria and progressive renal failure, and often accompanied by sensorineural hearing loss and ocular changes. Mutations in the genes encoding for three members of the type IV collagen protein family have been found to be the cause of the disease. We describe a large Turkish family with X-linked AS. We performed linkage analysis in this family and sequencing to identify the mutation in the proband whose disease was confirmed by renal biopsy.

After genomic DNAs extracted, linkage to the COL4A5 locus was examined using the 2B6 and 2B20, DXS1106, DXS1105 and COL4A5 markers. In addition, COL4A5 gene sequence analysis was performed in the proband.

Genetic linkage analysis demonstrated co-segregation of the disease. Haplotype analysis showed that the same haplotype was carried by all affected males and obligatory carrier females. Mutation analysis of the proband has revealed a novel nonsense mutation (c.1135C>T; Gln379X) in exon 19 of the COL4A5 gene which may lead to a more severe phenotype in affected family members carrying this mutation. According to GenBank data base, this mutation has not been reported previously.

Genetic testing identified a previously undescribed COL4A5 mutation as the cause of the disease.