A NOVEL MISSENSE MUTATION IN EXON-3 OF THE COL4A5 GENE ASSOCIATED WITH LATE-ONSET ALPORT SYNDROME

We have identified a novel missense transition (362G-->A) in exon 3 of the COL4A5 gene in a male patient with late-onset Alport syndrome. We used non-isotopic single strand conformation polymorphism, heterodupl ex analysis, and automated DNA sequencing. The mutation changes a cons erved glycine at codon 54 for an aspartic acid (Gly54Asp), which aboli shes a BstNI site. Using restriction analysis, we identified the heter ozygous carrier status in the two daughters of the proband. Our findin gs are in keeping with the hypothesis that slower progressive forms of Alport syndrome are more often associated with missense mutations rat her than large deletions or frameshifts. This is the first mutation de scribed in the N-terminus triple helical 7S domain of the COL4A5 gene in an Alport syndrome patient.