title: Three keratin gene mutations account for the majority of dominant simplex epidermolysis bullosa cases within the population of Ireland.
abstract: We have located three extended families in Ireland (population 3.5 million) 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 Mutat 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 keratin (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 present in the normal population. Within the three families, a total of 44 living persons with such mutations have been identified, providing a minimum prevalence estimate for the disease in the Irish population of approximately 1 in 80,000, compared to an overall estimated global incidence at birth for all forms of EB of 1 in 50,000. Therefore, these three mutations probably account for the majority of cases of EBS within this population.
authors.affiliation: Department of Genetics, Trinity College Dublin, Ireland.
authors.forename: M M
authors.initials: MM
authors.lastname: Humphries
authors.forename: F C
authors.initials: FC
authors.lastname: Mansergh
authors.forename: A S
authors.initials: AS
authors.lastname: Kiang
authors.forename: S A
authors.initials: SA
authors.lastname: Jordan
authors.forename: D M
authors.initials: DM
authors.lastname: Sheils
authors.forename: M J
authors.initials: MJ
authors.lastname: Martin
authors.forename: G J
authors.initials: GJ
authors.lastname: Farrar
authors.forename: P F
authors.initials: PF
authors.lastname: Kenna
authors.forename: M M
authors.initials: MM
authors.lastname: Young
authors.forename: P
authors.initials: P
authors.lastname: Humphries
mesh_terms: D000595:Amino Acid Sequence; D017124:Conserved Sequence; D016110:Epidermolysis Bullosa Simplex / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D007494:Ireland; D007633:Keratins / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation
chemical_list: D007633:Keratins