CRELD1基因在汉族先天性房室隔缺损患儿中的突变分析  

Analysis of CRELD1 gene mutations in Han Chinese patients with atrioventricular septal defect

作　　者：袁浪[1] 李波 郭颖[3] 赵武 吕拥芬[1] 黄敏[1] 李奋[3] 沈捷[1] 

机构地区：[1]上海市儿童医院上海交通大学附属儿童医院,上海200040 [2]中国南方基因中心,上海200032 [3]上海交通大学医学院附属上海儿童医学中心,上海200127

出　　处：《临床儿科杂志》2010年第12期1145-1148,共4页Journal of Clinical Pediatrics

基　　金：国家自然科学基金资助项目(No.30772348)

摘　　要：目的探讨CRELD1基因突变在房室间隔缺损(AVSD)发病机制中的作用。方法收集67例汉族AVSD患儿(包括合并21三体综合征10例)血液标本,PCR方法扩增CRELD1基因全部11个外显子编码序列后,对扩增产物进行测序,然后与GenBank人CRELD1基因编码序列进行比对,并以100名健康汉族人群为对照。结果在67例患儿中检出1例错义突变(碱基变化为G973A,氨基酸改变为E325K),为部分型AVSD伴21三体综合征的男性患儿;7例患儿发现基因多态性(rs 2302787,碱基变化C383G,氨基酸改变P128R);24例患儿发现基因多态性(rs 3774207,碱基变化C1119T,氨基酸编码H373H)。结论合并21三体综合征的AVSD患儿中,CRELD1基因突变的检出率(1/10例,10%)高于非综合征、散发的AVSD人群(0/57例,0%),但这一结论尚有待于更多的病例数证实;AVSD患儿中,CRELD1基因突变的检出率不高,提示AVSD可能是一个多基因的遗传性疾病。Objective To analyze the mutations of CRELD1 gene in Han Chinese patients with atrioventricular septal defect（AVSD）and investigate the relationship between CRELD1 gene and pathogenesis of AVSD.Methods Sixty-seven Han Chinese patients with AVSD（10 associated with Trisomy 21 syndrome and 57 were sporadic non-syndromic patients）were recruited in the study,100 healthy Han age-matched children were studied as controls.Encoding region and flanking exon of CRELD1 gene were amplified by polymerase chain reaction（PCR）,and sequenced with DNA fragment analysis system.The results were compared with the sequence of CRELD1 gene in GenBank.Results A novel missense mutation（cG973A,aa E325K）was identified in a patient with partial AVSD associated with Trisomy 21 syndrome.And polymorphism of the gene（c.C383G,aa P128R）from 7 patients and nonsense polymorphism（c.C1119T,aa H373H）from 24 patients were detected.Conclusions Prevalence of CRELD1 gene mutation was higher in AVSD patients associated with trisomy 21 syndrome than patients with sporadic AVSD（1/10 vs.0/57）,however,this finding needs further investigation with more samples.The low incidence of CRELD1 in patients with AVSD might suggest that AVSD is a polygenic disorder.

关 键 词：CRELD1基因 先天性心脏病 房室隔缺损 21三体综合征 

分 类 号：R725.4[医药卫生—儿科]