title: Epidermolytic hyperkeratosis type PS-1 caused by aberrant splicing of KRT1.
abstract: Mutations in the keratin 1 (KRT1) gene underlie epidermolytic hyperkeratosis (EHK). This autosomal dominant disorder is characterized by phenotypic heterogeneity. In the present study, we assessed a 33-year-old individual presenting with severe palmoplantar keratoderma and histopathological findings suggestive of EHK. We analysed genomic DNA extracted from the patient's blood lymphocytes for pathogenic mutations in KRT1. A heterozygous 4-bp deletion was identified in intron 1 of the gene (591+3_+6delGAGT), suggesting the possibility that it may interfere with the normal splicing of intron 1. We detected a 66-bp deletion in KRT1 mRNA extracted from the patient's skin, predicted to result in the translation of a mutant KRT1 lacking 22 amino acids, including the conserved helix initiation motif. The identification of this unusual and novel mutation underscores the diagnostic importance of sequence analysis of keratin gene noncoding regions.
authors.affiliation: Department of Dermatology and Laboratory of Molecular Dermatology, Rambam Medical Center, Haifa, and Mohs Surgery Unit, Assuta Medical Center, Tel Aviv, Israel.
authors.forename: O
authors.initials: O
authors.lastname: Tal
authors.forename: R
authors.initials: R
authors.lastname: Bergman
authors.forename: J
authors.initials: J
authors.lastname: Alcalay
authors.forename: M
authors.initials: M
authors.lastname: Indelman
authors.forename: E
authors.initials: E
authors.lastname: Sprecher
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D017353:Gene Deletion; D006801:Humans; D017488:Hyperkeratosis, Epidermolytic / Q000175:diagnosis / Q000235:genetics*; D053556:Keratin-1; D007633:Keratins / Q000235:genetics*; D007645:Keratoderma, Palmoplantar / Q000235:genetics*; D009154:Mutation; D012326:RNA Splicing / Q000235:genetics
chemical_list: C491616:KRT1 protein, human; D053556:Keratin-1; D007633:Keratins