A homozygous frameshift mutation in the HOXC13 gene underlies pure hair and nail ectodermal dysplasia in a Syrian family.

Muhammad Farooq, Mazen Kurban, Atsushi Fujimoto, Hiroki Fujikawa, Ossama Abbas, Georges Nemer, Jessica Saliba, Rima Sleiman, Mona Tofaili, Abdul-Ghani Kibbi, Masaaki Ito, Yutaka Shimomura

Laboratory of Genetic Skin Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Human mutation 2013 Apr

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Pure hair and nail ectodermal dysplasia (PHNED) is a rare genetic disorder characterized by hypotrichosis or complete alopecia, as well as nail dystrophy. Mutations in the type II hair keratin gene KRT85 and the HOXC13 gene on chromosome 12q have recently been identified in families with autosomal-recessive PHNED. In the present study, we have analyzed a consanguineous Syrian family with an affected girl having complete alopecia and nail dystrophy since birth. The family clearly showed linkage to chromosome 12q13.13-12q14.3, which excluded the KRT85 gene. Sequencing of another candidate gene HOXC13 within the linkage interval identified a homozygous frameshift mutation (c.355delC; p.Leu119Trpfs*20). Expression studies in cultured cells revealed that the mutant HOXC13 protein mislocalized within the cytoplasm, and failed to upregulate the promoter activities of its target genes. Our results strongly suggest crucial roles of the HOXC13 gene in the development of hair and nails in humans. © 2013 Wiley Periodicals, Inc.

Citation

Muhammad Farooq, Mazen Kurban, Atsushi Fujimoto, Hiroki Fujikawa, Ossama Abbas, Georges Nemer, Jessica Saliba, Rima Sleiman, Mona Tofaili, Abdul-Ghani Kibbi, Masaaki Ito, Yutaka Shimomura. A homozygous frameshift mutation in the HOXC13 gene underlies pure hair and nail ectodermal dysplasia in a Syrian family. Human mutation. 2013 Apr;34(4):578-81