DE-NOVO COL4A5 GENE-MUTATIONS IN ALPORTS-SYNDROME

Before the advent of direct molecular gene analysis the diagnosis of A lport syndrome was operationally based on three of the four classical clinical criteria. Recently, mutations have been identified in the COL 4A5 gene, which is involved in X-linked Alport syndrome. Here we descr ibe two de-novo mutations in two unrelated children, a male and a fema le, both with early onset of the nephropathy, but with only one of the diagnostic criteria, i.e. electronmicroscopy alterations. Because of the significant estimated proportion of de-novo mutations this diagnos is should be considered in children with early signs of nephropathy, e ven without a suggestive family history or clinical picture (ocular or audiologic abnormalities). In the future the diagnosis of Alport synd rome will probably be made on the basis of both clinical findings and molecular analysis. Now Alport syndrome is clearly underdiagnosed.