A Homozygous Frameshift Mutation in the HOXC13 Gene Underlies Pure Hair and Nail Ectodermal Dysplasia in a Syrian Family
A Homozygous Frameshift Mutation in the HOXC13 Gene Underlies Pure Hair and Nail Ectodermal Dysplasia in a Syrian Family
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DOI：
10.1002/humu.22271
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发表时间：
2013-04-01
期刊：
影响因子：
3.9
通讯作者：
Shimomura, Yutaka
中科院分区：
文献类型：
--
作者：
Farooq, Muhammad;Kurban, Mazen;Shimomura, Yutaka
单纯性毛发和指甲外胚层发育不良（PHNED）是一种罕见的遗传性疾病，其特征是毛发减少或完全脱发，以及指甲营养不良。最近在常染色体隐性PHNED家族中发现了染色体12 q上的II型头发角蛋白基因KRT 85和HOXC 13基因的突变。在本研究中，我们分析了一个叙利亚血缘家庭，一个受影响的女孩有完整的脱发和指甲营养不良，因为出生。该家系明确显示与染色体12q13.1312q14.3连锁，排除了KRT 85基因。对连锁区间内的另一个候选基因HOXC 13进行测序，发现了一个纯合移码突变（c.355delC; p.Leu119Trpfs*20）。在培养细胞中的表达研究表明，突变HOXC 13蛋白错误定位在细胞质中，并且未能上调其靶基因的启动子活性。我们的研究结果强烈表明HOXC 13基因在人类头发和指甲的发育中起着至关重要的作用。
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 12q13.1312q14.3, 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.