特发性肺动脉高压相关SOX17基因新突变分析

Novel mutations of SOX17 gene in patients with idiopathic pulmonary arterial hypertension

目的:寻找特发性肺动脉高压相关SOX17基因新突变。方法:收集58例特发性肺动脉高压患儿和200名健康对照者的临床资料及血标本,纯化基因组DNA。测序分析研究对象的SOX17基因以发现致特发性肺动脉高压突变。利用在线计算机程序分析突变氨基酸在物种进化上的保守性及其致病性。结果:在2例特发性肺动脉高压患儿中各发现1种SOX17基因新突变,分别为c.232T>A和c.281A>T突变,即p.Trp78Arg和p.His94Leu突变。该突变不存在于200名健康对照者。数据分析表明突变氨基酸在多物种进化上完全保守且均具有致病性。结论:特发性肺动脉高压相关SOX17基因新突变对特发性肺动脉高压患者的遗传咨询及精准防治具有潜在的临床意义。

Objective:To identify novel mutations in the SOX17 gene contributing to idiopathic pulmonary arterial hypertension(PAH).Methods:The clinical data and blood samples were collected from 58 unrelated children with idiopathic PAH and 200 healthy controls.Genomic DNA was purified from blood leucocytes.Sequencing analysis of the SOX17 gene was carried out for identification of novel mutation.The online software was used to analyze whether the mutated amino acid was evolutionarily conserved.The disease-causing potential of the identified mutation was also predicted.Results:Two novel SOX17 mutations,c.232T>A and c.281A>T,namely p.Trp78Arg and p.His94Leu,were identified in two unrelated children with idiopathic PAH,which was absent from 200 health control individuals.The altered amino acid was completely conserved evolutionarily across species,and the mutations were predicted to be pathogenic.Conclusions:The novel SOX17 mutation is involved in idiopanthic PAH,which has potential clinical implications for the genetic counseling and precise prevention and treatment of idiopanthic PAH.