Mutations in the Lipase H Gene Underlie Autosomal Recessive Woolly Hair/Hypotrichosis
Mutations in the Lipase H Gene Underlie Autosomal Recessive Woolly Hair/Hypotrichosis
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DOI：
10.1038/jid.2008.290
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发表时间：
2009-03-01
影响因子：
6.5
通讯作者：
Christiano, Angela M.
中科院分区：
文献类型：
--
作者：
Shimomura, Yutaka;Wajid, Muhammad;Christiano, Angela M.
羊毛状头发（WH）的特征是存在细而紧密卷曲的头发。WH可以表现为某些全身性疾病的症状，或没有相关发现（非综合征性WH）。非综合征性WH已知是以常染色体显性（OMIM 194300）或隐性（ARWH; OMIM 278150）性状遗传的。在这项研究中，我们确定了11个巴基斯坦血统的近亲家庭与ARWH，以及相关的功能，包括稀疏和色素减退的毛干。我们首先检查了P2 RY 5基因的突变，该基因编码一种孤儿G蛋白偶联受体，我们最近确定该受体是ARWH的原因。然而，这11个家族中没有一个在P2 RY 5基因上发生突变。为了确定疾病位点，我们在这些家庭中的一个使用Affytek 10 K阵列进行了连锁研究，并确定了染色体3q 27上的一个暗示连锁的区域。该区域含有脂肪酶H（LIPH）基因，最近已被证明是常染色体隐性遗传形式的低血糖的基础。突变分析导致在所分析的所有11个家族的LIPH中鉴定出总共5个致病性突变。这些结果表明，LIPH是ARWH/低血糖的第二个致病基因，引起临床上与P2 RY 5突变难以区分的表型。
Woolly hair (WH) is characterized by the presence of fine and tightly curled hair. WH can appear as a symptom of some systemic diseases, or without associated findings (nonsyndromic WH). Nonsyndromic WH is known to be inherited as either an autosomal-dominant (OMIM 194300) or recessive (ARWH; OMIM 278150) trait. In this study, we identified 11 consanguineous families of Pakistani origin with ARWH, as well as associated features including sparse and hypopigmented hair shafts. We first checked for mutations in the P2RY5 gene, which encodes an orphan G-protein-coupled receptor that we recently identified as a cause of ARWH. However, none of the 11 families had mutations in the P2RY5 gene. To identify the disease locus, we performed linkage studies in one of these families using the Affymetrix 10K array, and identified a region of suggestive linkage on chromosome 3q27. This region contains the lipase H (LIPH) gene which has been recently shown to underlie an autosomal-recessive form of hypotrichosis. Mutation analysis resulted in the identification of a total of 5 pathogenic mutations in the LIPH of all 11 families analyzed. These results show that LIPH is a second causative gene for ARWH/hypotrichosis, giving rise to a phenotype clinically indistinguishable from P2RY5 mutations.