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

Epidermolytic hyperkeratosis (EHK) is a hereditary skin disorder typified b y blistering due to cytolysis. One in 100,000 individuals is affected by th is autosomal-dominant disease. The onset of the disease phenotype is typica lly at birth. Histological and ultrastructural examination of the epidermis shows a thickened stratum corneum and tonofilament clumping around the nuc leus of suprabasal keratinocytes. Linkage studies localized the disease gen es 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 s uprabasal keratins, K1 and K10, have been reported in EHK patients. We have investigated a large kindred affected by EHK and identified a new point mu tation in the 2B region of keratin 1 (I107T), resulting from a T to C trans ition in codon 478.