1. Epithelial Genetics Group, Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, Pennsylvania, U.S.A.
2. ^*Department of Dermatology, Royal Victoria Hospital, Belfast, U.K.
3. ^†Department of Dermatology, Craigavon Area Hospital, Craigavon, U.K.
4. ^‡Department of Dermatology, Southern General Hospital, Glasgow, U.K.
5. ^§Division of Molecular Medicine, Belfast City Hospital, Belfast, U.K.
6. ^¶Department of Dermatology and Cutaneous Biology, Jefferson Institute for Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A.
7. ^**Department of Molecular and Cellular Pathology, Ninewells Medical School, Dundee, U.K.

Correspondence: Dr W.H. Irwin McLean, Department of Molecular and Cellular Pathology, Ninewells Medical School, Dundee DD1 9SY, U.K.

Received 25 October 1997; Revised 1 July 1998; Accepted 4 July 1998.

Abstract

Epidermolytic palmoplantar keratoderma (EPPK, MIM #144200) is an autosomal dominant disorder in which hyperkeratosis confined to the palms and soles is characterized histologically by cytolysis of suprabasal keratinocytes. Mutations in the keratin 9 gene (KRT9), a type 1 keratin expressed exclusively in the suprabasal keratinocytes of palmoplantar epidermis, have previously been demonstrated in this disorder. Here, we have studied four Northern Irish kindreds presenting with EPPK. By direct sequencing of polymerase chain reaction products, heterozygous missense mutations in exon 1 of KRT9 were detected in all the families. These included a novel mutation M156T; as well as M156V in two kindreds; and R162Q in the remaining family. All mutations were confirmed by reverse strand sequencing and restriction enzyme analysis. The point prevalence of EPPK in Northern Ireland was found to be 4.4 per 100,000. To date, all reported EPPK mutations occur in the helix initiation motif at the start of the central coiled-coil rod domain of K9.