Department of Biotechnology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Australas J Dermatol. 2011 Feb;52(1):37-42. doi: 10.1111/j.1440-0960.2010.00685.x. Epub 2010 Aug 24.
Hypohidrotic ectodermal dysplasia is an inherited disorder characterized by defective development of teeth, hairs and sweat glands. X-linked hypohidrotic ectodermal dysplasia is caused by mutations in the EDA gene, and autosomal forms of hypohidrotic ectodermal dysplasia are caused by mutations in either the EDAR or the EDARADD genes. To study the molecular genetic cause of autosomal recessive hypohidrotic ectodermal dysplasia in three consanguineous Pakistani families (A, B and C), genotyping of 13 individuals was carried out by using polymorphic microsatellite markers that are closely linked to the EDAR gene on chromosome 2q11-q13 and the EDARADD gene on chromosome 1q42.2-q43. The results revealed linkage in the three families to the EDAR locus. Sequence analysis of the coding exons and splice junctions of the EDAR gene revealed two mutations: a novel non-sense mutation (p.E124X) in the probands of families A and B and a missense mutation (p.G382S) in the proband of family C. In addition, two synonymous single-nucleotide polymorphisms were also identified. The finding of mutations in Pakistani families extends the body of evidence that supports the importance of EDAR for the development of hypohidrotic ectodermal dysplasia.
少汗型外胚层发育不良是一种遗传性疾病，其特征为牙齿、毛发和汗腺发育不全。X 连锁少汗型外胚层发育不良是由 EDA 基因突变引起的，而常染色体隐性遗传型少汗型外胚层发育不良则是由 EDAR 或 EDARADD 基因突变引起的。为了研究三个巴基斯坦近亲家族（A、B 和 C）常染色体隐性遗传型少汗型外胚层发育不良的分子遗传病因，对 13 名个体进行了基因分型，所用的多态性微卫星标记与染色体 2q11-q13 上的 EDAR 基因和染色体 1q42.2-q43 上的 EDARADD 基因紧密连锁。结果显示，这三个家族与 EDAR 基因座连锁。对 EDAR 基因的编码外显子和剪接接头进行序列分析发现了两个突变：A 组和 B 组先证者中存在新的无义突变（p.E124X），C 组先证者中存在错义突变（p.G382S）。此外，还鉴定出两个同义单核苷酸多态性。在巴基斯坦家族中发现的突变进一步证实了 EDAR 对少汗型外胚层发育不良发生的重要性。
