摘要
目的探讨活化素受体样激酶1(ALK1)基因、骨形成蛋白Ⅱ型受体(BMPR2)基因突变与儿童特发性肺动脉高压(IPAH)之间的关系。方法收集14例临床诊断为IPAH患儿及其部分家族成员的DNA样本,对ALK1、BMPR2基因启动子及外显子区域进行二代测序,测序结果与GenBank人ALK1、BMPR2基因序列进行分析比对,对存在突变的基因进行一代测序验证。另收集106例健康儿童作为对照组。结果 1例女性IPAH患儿ALK1基因外显子3发生错义突变(c.77 C>T:p.P 26 L);经数据库HMGD查对为一新突变位点。在1例女性患儿BMPR2基因外显子11发现错义突变(c.1447T>C:p.C483R),1例男性患儿母亲BMPR2基因外显子5 splicing区域发现错义突变(c.621+8T>C),1例女性患儿母亲BMPR2基因外显子10发现错义突变(c.1322G>A:p.G441E),以上突变在既往文献中均已有报道。结论在我国汉族IPAH患儿中首次发现ALK1基因外显子3错义突变,该新错义突变可能和IPAH形成有关。
Objective To explore the relationship of mutations in activin receptor-like kinase 1 gene(ALK1)and bone morphogenetic protein receptorⅡgene(BMPR2)with childhood idiopathic pulmonary arterial hypertension(IPAH).Methods The DNA sample from 14 pediatric patients diagnosed clinically of IPAH and some of their family members were collected.The promoters and exons of ALK1 and BMPR2 gene were directly sequenced by the next generation sequencing.The results were compared with the sequence of ALK1and BMPR2 gene in GenBank.The mutant genes were verified by first generation sequencing.One hundred and six healthy children were recruited as controls.Results A missense mutation in exon 3 of ALK1 gene(c.77C>T:p.P26L)was detected in one female IPAH patient,which is a new mutation site after searching database of HMGD.A missense mutation in exon 11 of BMPR2(c.1447T>C:p.C483R)was detected in a female patient,a missense mutation in exon 5 of BMPR2(c.621+8T>C)was detected in a male patient’s mother,and a missense mutation in exon 10 of BMPR2(c.1322G>A:p.G441E)was detected in a female patient’s mother.These 3 missense mutations had been reported.Conclusions A missense mutation in exon 3 of ALK1 gene is first discovered in IPAH patient of Han nationality,which may be responsible for the development of IPAH.
作者
王迎
李谧
吴晓云
吴良宇
刘玲娟
田杰
WANG Ying;LI Mi;WU Xiaoyun;WU Lingyu;LIU Lingjuan;TIAN Jie(Department of Cardiology,Children’s Hospital of Chongqing Medical University,Ministry of Education Key Laboratory of Child Development and Disorders,China International Science and Technology Cooperation Base of Child Development and Critical Disorders,Chongqing Key Laboratory of Pediatrics,Cho)
出处
《临床儿科杂志》
CAS
CSCD
北大核心
2018年第7期497-500,共4页
Journal of Clinical Pediatrics
基金
重庆市社会民生科技创新专项项目(No.cstc2015shmszx120043)
重庆医科大学附属儿童医院临床罕见疑难病专项(No.hjyn2013-5)