3 KERATIN GENE-MUTATIONS ACCOUNT FOR THE MAJORITY OF DOMINANT SIMPLEXEPIDERMOLYSIS-BULLOSA CASES WITHIN THE POPULATION OF IRELAND

We have located three extended families in Ireland (population 3.5 mil lion) with autosomal dominant simplex forms of Epidermolysis Bullosa ( EBS). A mutation within the keratin type I (K14) gene (Met-->272-->Arg ) in one family suffering from the generalized simplex (Koebner) form of the disease has been previously described (Humphries et al., Hum Mu tat 2:37-42, 1993). Here we report on the identification of mutations within the remaining two families, both of whom suffer from the Weber- Cockayne form of the disease. These mutations, within the type II kera tin (K5) gene, are Asn-->193-->Lys and Met-->327-->Thr. They have been shown in each case to co-segregate with the disease and are not prese nt in the normal population. Within the three families, a total of 44 living persons with such mutations have been identified, providing a m inimum prevalence estimate for the disease in the Irish population of approximately 1 in 80,000, compared to an overall estimated global inc idence at birth for all forms of EB of 1 in 50,000. Therefore, these t hree mutations probably account for the majority of cases of EBS withi n this population. (C) 1996 Wiley-Liss, Inc.