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 Printable version |
Identification of a de novo keratin 1 mutation in epidermolytic hyperkeratosis with palmoplantar involvement |
European Journal of Dermatology. Volume 16, Number 5, 507-10, September-October 2006, Genes and skin
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 Free Article
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Author(s) : Andrea Math, Jorge Frank, Alessandra Handisurya, Pamela Poblete-Gutiérrez, Katharina Slupetzky, Dagmar Födinger, Dorian Winter, Georg Stingl, Reinhard Kirnbauer |
Summary : Epidermolytic hyperkeratosis (EHK) (OMIM 113800) is a generalized skin disease with mostly autosomal dominant inheritance, caused by mutations in keratin 1 or keratin 10. These genes are expressed in suprabasal epidermal layers, resulting in abnormal keratin-intermediate filament cytoskeleton. We present a male patient with generalized hyperkeratosis involving palms and soles. In lesional skin massive hyperkeratosis and cytolysis in the suprabasal layers of the epidermis were observed. Immunohistochemistry staining for keratin 1 (and keratin 10) showed abnormal clumping in suprabasal keratinocytes. By electron microscopy perinuclear intermediate filament clumps were detected in the keratinocytes. A heterozygous missense mutation, designated L187F, was identified in exon 1 of the keratin 1 gene by direct sequencing. This mutation was not detected in his unaffected parents, indicative of a de novo mutational event. The homologous mutation (L187F, also designated L7F) in basal keratin genes keratin 5 or -14 causes epidermolysis bullosa simplex. The amount of keratin 1-mRNA in the patient’s skin was not altered compared to controls.We propose that the severe EHK phenotype observed in our patient results from a dominant negative effect of the L187F mutant Keratin 1 allele exerted on keratin 10, the associated partner-keratin. These findings should be helpful for genetic counseling, prenatal diagnosis and studying molecular structure-function relationship in EHK. |
Keywords : epidermolytic hyperkeratosis, genetics, genodermatosis, intermediate filaments, keratinizing disorder, keratin 1 |
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