Epidermolytic palmoplantar keratoderma caused by activation of a cryptic splice site in KRT9

Authors

  • D. Fuchs-Telem,

    1. Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
    2. Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
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  • G. Padalon-Brauch,

    1. Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
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  • O. Sarig,

    1. Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
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  • E. Sprecher

    Corresponding author
    1. Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
    • Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
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  • Conflict of interest: none declared.

Correspondence: Dr Eli Sprecher, Department of Dermatology, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel

E-mail: elisp@tasmc.health.gov.il

Summary

Epidermolytic palmoplantar keratoderma (EPPK) is caused by mutations in KRT9 and less often, KRT1. All known mutations in KRT9 have been found in regions of the gene encoding the conserved central α-helix rod domain. In the present study, we investigated the molecular basis of EPPK in a patient of Ashkenazi Jewish origin. The patient was found to carry a novel missense mutation in KRT9, resulting in the substitution of a poorly conserved leucine for valine at position 11 of the amino acid sequence. Despite its unusual location, the mutation was shown to be pathogenic through activation of a cryptic donor splice site, resulting in the deletion of 162 amino acids. The present data indicate the need to screen keratin genes in their entirety, as mutations altering domains of lesser functional importance may exert their deleterious effect at the transcriptional level.

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