title: A homozygous frameshift mutation in the HOXC13 gene underlies pure hair and nail ectodermal dysplasia in a Syrian family.
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.
authors: Laboratory of Genetic Skin Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors: Muhammad
authors: M
authors: Farooq
authors: Mazen
authors: M
authors: Kurban
authors: Atsushi
authors: A
authors: Fujimoto
authors: Hiroki
authors: H
authors: Fujikawa
authors: Ossama
authors: O
authors: Abbas
authors: Georges
authors: G
authors: Nemer
authors: Jessica
authors: J
authors: Saliba
authors: Rima
authors: R
authors: Sleiman
authors: Mona
authors: M
authors: Tofaili
authors: Abdul-Ghani
authors: AG
authors: Kibbi
authors: Masaaki
authors: M
authors: Ito
authors: Yutaka
authors: Y
authors: Shimomura
mesh_terms: D000505:Alopecia; D000595:Amino Acid Sequence; D001483:Base Sequence; D003241:Consanguinity; D004476:Ectodermal Dysplasia / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006197:Hair / Q000473:pathology*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D007223:Infant; D009262:Nails / Q000473:pathology*; D010375:Pedigree; D010641:Phenotype; D020161:Physical Chromosome Mapping; D013593:Syria
chemical_list: C410305:HOXC13 protein, human; D018398:Homeodomain Proteins