VARIABILITY OF CLINICAL PHENOTYPE IN A LARGE ALPORT FAMILY WITH GLY-1143-SER CHANGE OF COLLAGEN ALPHA-5(IV)-CHAIN

In a large Italian family with adult-onset Alport syndrome, molecular analysis of the COL4A5 gene, which encodes the alpha 5(IV)-chain of gl omerular basement membrane collagen, revealed a GGC --> AGC change in exon 38, resulting in substitution of a serine for a glycine in positi on 1143 of the polypeptide chain, between interruptions 19 and 20 of t he triple helical domain. The mutation leads to loss of a restriction site for the enzyme Msp I, and could thus be easily recognized in seve ral female and male relatives. Among relatives of both sexes who carri ed the same mutation, the clinical phenotype of Alport syndrome was va riable as for the onset of renal failure and the presence of associate d ear and eye abnormalities.