1. Center for Cutaneous Research, St. Bartholomews and the Royal London School of Medicine and Dentistry, Queen Mary College, London, U.K.;
2. ^*Department of Cell and Molecular Pathology, St. John's Institute of Dermatology, St. Thomas Hospital, London, U.K.;
3. ^†Department of Medical Biosciences, Medical Genetics, Umea University, Sweden;
4. ^‡Department of Dermatology, Southern General Hospital, Glasgow, U.K.

Correspondence: Dr David P. Kelsell, Center for Cutaneous Research, St. Bartholomews and the Royal London School of Medicine and Dentistry, Queen Mary College, 2 Newark Street, London E1 2AT, U.K. Email: kelsell@icrf.icnet.uk

Received 25 September 2000; Revised 13 January 2001; Accepted 15 January 2001.

Abstract

We report a novel mutation in the exon 6 splice donor site of keratin 1 (G4134A) that segregates with a palmoplantar keratoderma in three kindreds. The nucleotide substitution leads to the utilization of a novel in-frame splice site 54 bases downstream of the mutation with the subsequent insertion of 18 amino acids into the 2B rod domain. This mutation appears to have a milder effect than previously described mutations in the helix initiation and termination sequence on the function of the rod domain, with regard to filament assembly and stability. Affected individuals displayed only mild focal epidermolysis in the spinous layer of palmoplantar epidermis, in comparison with cases of bullous congenital ichthyosiform erythroderma also due to keratin 1 mutations, which show widespread and severe epidermolysis. This study describes a novel mutation in KRT1 that results in a phenotype distinct from classical bullous congenital ichthyosiform erythroderma.