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Mutation L437P in the 2B domain of keratin 1 causes diffuse palmoplantar keratoderma in a Chinese pedigree
Author(s) -
Liu XP,
Ling J,
Xiong H,
Shi XL,
Sun X,
Pan Q,
Hu ZM,
Wu LQ,
Liang DS,
Long ZG,
Dai HP,
Xia JH,
Xia K
Publication year - 2009
Publication title -
journal of the european academy of dermatology and venereology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.655
H-Index - 107
eISSN - 1468-3083
pISSN - 0926-9959
DOI - 10.1111/j.1468-3083.2009.03175.x
Subject(s) - genodermatosis , plakoglobin , missense mutation , palmoplantar keratoderma , keratin 6a , hyperkeratosis , keratin , mutation , genetics , mutant , intermediate filament , medicine , gene , biology , cytoskeleton , wnt signaling pathway , cell , catenin
Diffuse palmoplantar keratoderma (DPPK) is an autosomal dominant genodermatosis characterized by uniform hyperkeratosis of the palm and sole epidermis. This disorder can be caused by mutations in the genes keratin 1 , keratin 9 , keratin 16 , desmoglein 1 and plakoglobin . Here we present a DPPK Chinese pedigree and identify the aetiology as a novel missense mutation, L437P, located in a highly conserved helix motif in domain 2B of KRT1. Functional analysis shows that overexpression of the L437P mutant in cultured cells leads to abnormal intermediate filament networks and filament aggregation. This gain‐of‐function mutation highlights the role of domain 2B in mediating filament assembly. Conflicts of interest The authors declare that they have no actual or potential conflicts of interest to disclose. Appropriate approval and procedures were used concerning human subjects.