A COMMON KERATIN-5 GENE MUTATION IN EPIDERMOLYSIS-BULLOSA SIMPLEX WEBER-COCKAYNE

The Weber-Cockayne subtype of epidermolysis bullosa simplex is an inherited skin-fragility disorder characterized by basal keratinocyte lysis and epidermal blistering confined primarily to the hands and feet. The disorder results from a mutation in either the keratin 5 or keratin 14 gene, which encode the peptide components of the obligate heterodimeric keratin intermediate filaments of the basal cell, We have determined that a T --> G substitution mutation in keratin 5, which results in a Ile --> Ser change at codon 161, is common among patients with the Weber-Cockayne disease variant, accounting for six of 13 cases tested. The observed high frequency of this mutation may result from either a mutational hot spot or a founder effect. The potential utility of this common mutation in confirming disease status in some at-risk individual is discussed.