Department of Medical Genetics, Oslo University Hospital, Oslo 0450, Norway.
Faculty of Medicine, University of Oslo, Oslo 0316, Norway.
Genes (Basel). 2016 Jul 27;7(8):41. doi: 10.3390/genes7080041.
We report on two brothers with visual impairment, and non-syndromic alopecia in the elder proband. The parents were first-degree Pakistani cousins. Whole exome sequencing of the elder brother and parents, followed by Sanger sequencing of all four family members, led to the identification of the variants responsible for the two phenotypes. One variant was a homozygous nonsense variant in the inhibitory subunit of the cone-specific cGMP phosphodiesterase gene, PDE6H:c.35C>G (p.Ser12*). PDE6H is expressed in the cones of the retina, which are involved in perception of color vision. This is the second report of a homozygous PDE6H:c.35C>G variant causing incomplete achromatopsia (OMIM 610024), thus strongly supporting the hypothesis that loss-of-function variants in PDE6H cause this visual deficiency phenotype. The second variant was a homozygous missense substitution in the lysophosphatidic acid receptor 6, LPAR6:c.188A>T (p.Asp63Val). LPAR6 acts as a G-protein-coupled receptor involved in hair growth. Biallelic loss-of-function variants in LPAR6 cause hypotrichosis type 8 (OMIM 278150), with or without woolly hair, a form of non-syndromic alopecia. Biallelic LPAR6:c.188A>T was previously described in five families from Pakistan.
我们报告了两兄弟的视力障碍和先证者的非综合征性脱发。父母是表亲关系。对哥哥和父母进行全外显子组测序，然后对所有 4 名家庭成员进行 Sanger 测序，确定了导致这两种表型的变异。一个变异是锥细胞特异性环磷酸鸟苷磷酸二酯酶基因抑制亚基 PDE6H 中的纯合无义变异，c.35C>G（p.Ser12*）。PDE6H 在视网膜的锥体中表达，锥体参与色觉感知。这是第二个报道的纯合 PDE6H:c.35C>G 变异导致不完全色盲（OMIM 610024）的病例，因此强烈支持 PDE6H 中的功能丧失变异导致这种视觉缺陷表型的假说。第二个变异是在溶血磷脂酸受体 6（LPAR6）中的纯合错义替换，c.188A>T（p.Asp63Val）。LPAR6 作为一种 G 蛋白偶联受体，参与毛发生长。LPAR6 的双等位基因功能丧失变异导致少毛症 8 型（OMIM 278150），伴有或不伴有羊毛状头发，是一种非综合征性脱发。双等位基因 LPAR6:c.188A>T 以前在来自巴基斯坦的五个家庭中描述过。
