A Homozygous Frameshift Mutation in the HOXC13 Gene Underlies Pure Hair and Nail Ectodermal Dysplasia in a Syrian Family

Authors

  • Muhammad Farooq,

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

    1. Department of Dermatology, American University of Beirut Medical Center, Beirut, Lebanon
    2. Department of Biochemistry and Molecular Genetics, American University of Beirut Medical Center, Beirut, Lebanon
    3. Department of Dermatology, Columbia University, New York City, New York
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    • These authors equally contributed to this work.

  • Atsushi Fujimoto,

    1. Laboratory of Genetic Skin Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
    2. Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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  • Hiroki Fujikawa,

    1. Laboratory of Genetic Skin Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
    2. Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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  • Ossama Abbas,

    1. Department of Dermatology, American University of Beirut Medical Center, Beirut, Lebanon
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  • Georges Nemer,

    1. Department of Biochemistry and Molecular Genetics, American University of Beirut Medical Center, Beirut, Lebanon
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  • Jessica Saliba,

    1. Department of Biochemistry and Molecular Genetics, American University of Beirut Medical Center, Beirut, Lebanon
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  • Rima Sleiman,

    1. Department of Dermatology, American University of Beirut Medical Center, Beirut, Lebanon
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  • Mona Tofaili,

    1. Department of Biochemistry and Molecular Genetics, American University of Beirut Medical Center, Beirut, Lebanon
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  • Abdul-Ghani Kibbi,

    1. Department of Dermatology, American University of Beirut Medical Center, Beirut, Lebanon
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  • Masaaki Ito,

    1. Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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  • Yutaka Shimomura

    Corresponding author
    • Laboratory of Genetic Skin Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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    • These authors equally contributed to this work.


  • Communicated by Sergio Ottolenghi

  • Contract grant sponsors: Ministry of Education, Culture, Sports, Science and Technology, Japan; American University of Beirut, Lebanon (DER.MK.01).

Correspondence to: Yutaka Shimomura, Laboratory of Genetic Skin Diseases, Niigata University Graduate School of Medical and Dental Sciences, 1–757 Asahimachi-dori, Chuo-ku, Niigata 951–8510, Japan. E-mail: yshimo@med.niigata-u.ac.jp

ABSTRACT

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.

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