Center for Translational Genetics, Rappaport Institute for Research in the Medical Sciences, Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
Clin Exp Dermatol. 2011 Mar;36(2):188-94. doi: 10.1111/j.1365-2230.2010.03944.x. Epub 2010 Nov 10.
Autosomal recessive hypotrichosis simplex (ARHS) presents with progressive hair loss mainly affecting the scalp area. In a small number of families, the condition has been associated with mutations in three distinct genes: DSG4, LIPH and LPAR6.
To identify the molecular basis of ARHS in a consanguineous family of Turkish extraction.
We used a combination of microsatellite marker screening and direct sequencing.
We identified a novel missense mutation (c.C587T) in the human LPAR6 gene, resulting in the amino acid substitution p.P196L. The mutation affects a highly conserved amino acid residue, and is predicted to disrupt signalling through the P2Y5 receptor.
This study provides further evidence supporting a role for the lysophosphatidyl signalling pathway in hair growth and differentiation. In addition, this paper reports, for the first time to our knowledge, the use of homozygosity mapping as a premutation screening tool in the diagnosis of a group of inherited hair disorders.
常染色体隐性单纯性毛发稀少症（ARHS）表现为进行性脱发，主要影响头皮区域。在少数家庭中，该病症与三个不同基因的突变有关：DSG4、LIPH 和 LPAR6。
鉴定一个土耳其血统近亲家族 ARHS 的分子基础。
我们使用微卫星标记筛选和直接测序的组合。
我们在人类 LPAR6 基因中发现了一个新的错义突变（c.C587T），导致氨基酸取代 p.P196L。该突变影响高度保守的氨基酸残基，预计会破坏 P2Y5 受体的信号传递。
本研究进一步证实了溶血磷脂信号通路在头发生长和分化中的作用。此外，本文首次报道了利用纯合子作图作为一组遗传性毛发疾病的先证者筛查工具。
