Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Pakistan.
Eur J Dermatol. 2010 Jul-Aug;20(4):443-6. doi: 10.1684/ejd.2010.0962. Epub 2010 Apr 21.
Hair-nail ectodermal dysplasia (HNED; OMIM 602032) constitutes a rare subgroup of ectodermal dysplasias characterised by onychodystrophy, hypotrichosis and brittle hair. We identified a large consanguineous Pakistani family with four siblings affected by a congenital autosomal recessive form of the disease. Based on previous genetic findings in HNED we performed linkage analysis in the family using chromosome 12 markers. A genetic linkage analysis revealed a lod score of 2.92 ( = 0.0) at locus D12S368, indicating the disease gene to be located on chromosome 12. Candidate genes on chromosome 12, including the KRTHB5 gene and four additional keratin II genes, were sequenced in affected family members. Sequence analysis of the coding regions of keratin KRTHB5 gene, previously associated with a distinct clinical form of hair-nail dysplasia, revealed normal coding regions. Our study confirms linkage of a variant clinical form of hair-nail ectodermal dysplasia to chromosome 12 without any mutation in the coding sequences of the KRTHB5 gene. The results suggest this family to have either a non-coding mutation in the KRTHB5 gene, or a mutation in a yet unknown gene within the linked region on chromosome 12.
毛发-指甲外胚层发育不全症（HNED；OMIM 602032）是一种罕见的外胚层发育不全症亚组，其特征为甲营养不良、毛发稀疏和脆弱。我们鉴定了一个有 4 名受影响同胞的大型巴基斯坦近亲家族，他们患有先天性常染色体隐性疾病。基于之前在 HNED 中的遗传发现，我们使用 12 号染色体标记物对该家族进行了连锁分析。遗传连锁分析显示在 D12S368 位点的 lod 得分为 2.92（ = 0.0），表明疾病基因位于 12 号染色体上。对 12 号染色体上的候选基因，包括 KRTHB5 基因和另外 4 个角蛋白 II 基因，在受影响的家族成员中进行了测序。先前与独特的毛发-指甲发育不良临床表型相关的角蛋白 KRTHB5 基因的编码区序列分析显示正常编码区。我们的研究证实了一种变异的毛发-指甲外胚层发育不全症与 12 号染色体的连锁，而 KRTHB5 基因的编码序列没有任何突变。结果表明该家族要么在 KRTHB5 基因的非编码区存在突变，要么在 12 号染色体连锁区域存在未知基因的突变。
