1例羊毛状发家系脂肪酶H基因检测

Detection of Lipase-H Gene in a Family with Woolly Hair

目的对1例散发羊毛状发家系进行G蛋白偶联受体(purinergic receptor P2Y,G protein-coupled 5,P2RY5)和脂肪酶H(lipase-H,LIPH)基因检测,以明确其致病机制。方法收集患者的毛发和外周静脉血液,及家系中3例正常人和100例非家系成员外周血。提取基因组脱氧核糖核酸(deoxyribonucleic acid,DNA),聚合酶链式反应(polymerase chain reaction,PCR)扩增P2RY5和LIPH基因所有外显子及其侧翼序列,扩增产物直接双向测序,结果与GenBank中登记序列进行比对分析,查找有无突变基因。结果该家系患者未发现P2RY5基因突变,而在LIPH基因发现一新的杂合性错义突变c.454G>A(p.G152R),导致第152位甘氨酸被精氨基酸替代。而家系中3例正常人和100例无关人群基因组DNA检测测序结果未发现相同碱基突变。结论报告了羊毛状发LIPH基因的杂合突变,扩大了LIPH基因突变库。该结果进一步支持LIPH/溶血磷脂酸(lysophosphatidic acid,LPA)/P2Y5信号转导通路在人类毛发生长中的关键作用。

Objective To search for pathogenic mutations in genes P2RY5 and lipase-H （LIPH） in a Chinese patient with woolly hair phenotype. Methods Blood samples were obtained from the patient and three unafffected individuals in the family as well as from 100 normal human controls. Genomic deoxyribonucleic acid （DNA） were extracted and subjected to polymerase chain reaction （PCR） for the amplification of the entire encoding and flanking sequences of P＇2RY5 and LIPH gene, followed by bidirectional sequencing. Finally, the sequences were compared with those in GenBank with BLAST software. Results No mutation was detected in P2RY5 gene, while a novel heterozygous missense mutation, c.454G〉A （p. GI52R） was identified in the LIPH gene of the patient, which would lead to a substitution of glycine by an arginine residue at amino acid 152 （p.G152R）. The same nucleotide mutation was not found in the other three individuals and 100 unrelated controls. Conclusion We report the first heterozygous mutation in the LIPH gene in a Chinese patient with woolly hair phenotype, which extends the repertoire of LIPH mutations, and further supports a crucial role of LIPH/LPA/P2Y5 signalling pathway in hair growth in humans.