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Epidermolytic hyperkeratosis type PS‐1 caused by aberrant splicing of KRT1
Author(s) -
Tal O.,
Bergman R.,
Alcalay J.,
Indelman M.,
Sprecher E.
Publication year - 2005
Publication title -
clinical and experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.587
H-Index - 78
eISSN - 1365-2230
pISSN - 0307-6938
DOI - 10.1111/j.1365-2230.2004.01661.x
Subject(s) - biology , epidermolytic hyperkeratosis , genetics , gene , intron , hyperkeratosis , rna splicing , palmoplantar keratoderma , microbiology and biotechnology , rna
Summary 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.