Naeem M, Wajid M, Lee K, Leal S M, Ahmad W
J Med Genet. 2006 Mar;43(3):274-9. doi: 10.1136/jmg.2005.033381.
Ectodermal dysplasias are developmental disorders affecting tissues of ectodermal origin. To date, four different types of ectodermal dysplasia involving only hair and nails have been described. In an effort to understand the molecular bases of this form of ectodermal dysplasia, large Pakistani consanguineous kindred with multiple affected individuals has been ascertained from a remote region in Pakistan.
To identify the gene underlying the phenotype.
Microsatellite markers were genotyped in candidate regions and two point and multipoint parametric linkage analysis carried out.
The disease locus was mapped to a 16.6 centimorgan region on chromosome 12q12-q14.1 (Zmax = 8.2), which harbours six type II hair keratin genes. DNA sequence analysis revealed a homozygous missense mutation in the hair matrix and cuticle keratin KRTHB5, leading to histidine substitution of a conserved arginine residue (R78H) located in the head domain.
This report provides the first direct evidence relating to the molecular pathogenesis of pure hair-nail ectodermal dysplasias.
外胚层发育异常是影响外胚层来源组织的发育障碍。迄今为止，已描述了仅涉及毛发和指甲的四种不同类型的外胚层发育异常。为了了解这种形式的外胚层发育异常的分子基础，已从巴基斯坦的一个偏远地区确定了一个有多个患病个体的大型巴基斯坦近亲家系。
确定该表型的致病基因。
对候选区域的微卫星标记进行基因分型，并进行两点和多点参数连锁分析。
疾病基因座定位于12号染色体q12-q14.1上的一个16.6厘摩区域（Zmax = 8.2），该区域包含六个II型毛发角蛋白基因。DNA序列分析显示毛发基质和角质层角蛋白KRTHB5存在纯合错义突变，导致位于头部结构域的保守精氨酸残基（R78H）被组氨酸取代。
本报告提供了有关纯毛发-指甲外胚层发育异常分子发病机制的首个直接证据。
