Identification of a novel mutation in keratin 1 in a family with epidermolytic hyperkeratosis

Abstract: Epidermolytic hyperkeratosis (EHK) is a hereditary skin disorder typified by blistering due to cytolysis. One in 100,000 individuals is affected by this autosomal-dominant disease. The onset of the disease phenotype is typically at birth. Histological and ultrastructural examination of the epidermis shows a thickened stratum corneum and tonofilament clumping around the nucleus of suprabasal keratinocytes. Linkage studies localized the disease genes on chromosomes 12q and 17q which contain the type II and type I keratin gene clusters. Recently, several point mutations in the genes encoding the suprabasal keratins, K1 and K10, have been reported in EHK patients. We have investigated a large kindred affected by EHK and identified a new point mutation in the 2B region of keratin 1 (I107T), resulting from a T to C transition in codon 478