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A Homozygous Frameshift Mutation in the HOXC13 Gene Underlies Pure Hair and Nail Ectodermal Dysplasia in a Syrian Family
Author(s) -
Farooq Muhammad,
Kurban Mazen,
Fujimoto Atsushi,
Fujikawa Hiroki,
Abbas Ossama,
Nemer Georges,
Saliba Jessica,
Sleiman Rima,
Tofaili Mona,
Kibbi AbdulGhani,
Ito Masaaki,
Shimomura Yutaka
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22271
Subject(s) - biology , ectodermal dysplasia , frameshift mutation , genetics , nail (fastener) , mutation , gene , coffin , anatomy , materials science , metallurgy
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 S yrian 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.