Human Molecular Genetics Laboratory, National Institute for Biotechnology and Genetic Engineering, Faisalabad, Pakistan.
Eur J Dermatol. 2012 Jul-Aug;22(4):464-6. doi: 10.1684/ejd.2012.1731.
Mutations in the lysophosphatidic acid receptor 6 (LPAR6) gene cause localized autosomal recessive hypotrichosis. We report six consanguineous families from Pakistan with segregating hypotrichosis localized to the scalp. Genetic investigation using polymorphic microsatellite markers revealed homozygosity spanning the LAH3 locus on chromosome 13 in affected individuals of all six families. Sequence analysis of the LPAR6 gene showed a novel insertion resulting in a frameshift and a premature termination (p.I194FfsX11) in affected members of one family. In the remaining five families we identified a previously described missense mutation (p.G146R) in a homozygous state in affected members. The closest flanking polymorphic marker showed an identical allele size in the five families segregating with the p.G146R mutation, supporting a single origin of this variation. These findings extend the spectrum of known LPAR6 mutations and suggest a founder effect of the p.G146R mutation in the Pakistani population.
LPAR6 基因中的突变导致局部常染色体隐性少毛症。我们报道了来自巴基斯坦的六个有亲缘关系的家族，其头皮局部少毛症呈常染色体隐性遗传。使用多态微卫星标记的遗传研究显示，所有六个家族的受累个体均存在跨越 13 号染色体 LAH3 基因座的纯合子。LPAR6 基因的序列分析显示，一个新的插入导致移码和过早终止（p.I194FfsX11），一个家族的受累成员存在该突变。在其余五个家族中，我们在受累成员中发现了一个先前描述的错义突变（p.G146R），呈纯合状态。与 p.G146R 突变分离的五个家族中，最近的侧翼多态性标记显示出相同的等位基因大小，支持该变异的单一起源。这些发现扩展了已知 LPAR6 突变的范围，并提示巴基斯坦人群中 p.G146R 突变存在一个奠基者效应。
