一个先天性主动脉瓣上狭窄家系的分子遗传性分析  

Molecular genetic analysis of a Chinese family with congenital supravaivular aortic stenosis

作　　者：卢超霞[1] 张慧[2] 杨威[1] 

机构地区：[1]中国医学科学院基础医学研究所,麦库西克-张孝骞协和遗传医学中心,北京100005 [2]北京协和医学院八年制临床医学专业2001级,100005

出　　处：《国际遗传学杂志》2011年第3期127-129,134,共4页International Journal of Genetics

基　　金：基金项目：国家自然科学基金（81000783）

摘　　要：目的检测一个临床诊断为“先天性升主动脉狭窄”家系患者的基因组拷贝数变异，明确其发病的遗传学基础。方法以一个先天性升主动脉狭窄家系为研究对象，收集患儿及其患病父亲、正常母亲外周血标本，常规提取基因组DNA。应用Affymetrix人类全基因组SNP6．0芯片对患儿及l例正常健康对照个体进行检测，应用实时定量PCR（real—timequantitative polymerase—chain—reaction，qPCR）方法对芯片分析结果进行验证。结果经AffymetrixSNP6．0芯片分析显示患儿染色体7q11．23区域内弹力蛋白基因（elastin，ELN）5’端大部分及基因上游区域共约80kb发生杂合性缺失。在ELN基因内设计4对qPCR引物，在家系内进行验证，结果显示ELN的缺失向下游至少累及至第22外显子，且患儿父亲携带与患儿相同的杂合性缺失。结论ELN基因部分杂合性缺失为该患儿及其父亲发病的原因，二者之先天异常为主动脉瓣上狭窄（supravalvularaorticstenosis，SVAS）。Objective To detect the copy number variations （ CNVs ） in a family with congenital narrowing of the ascending aorta, and to explore the underlying genetic causes of the disease. Methods Peripheral blood samples were collected from an affected boy, his affected father and his apparently normal mother. Genomic DNA was extracted and genotyped using Affymetrix Genome-Wide Human SNP Array 6.0. CNVs were confirmed by real-time quantitative PCR （ qPCR ） . Results Our SNP Array 6. 0 analysis showed in the boy an about 80 kb heterozygous deletion affecting part of the elastin gene （ELN） . Further qPCR assays for four confirmed the presence of the deletion in the boy and his father, and indica- ted that the deletion involved at least the first 22 ELN exons. Conclusion A heterozygous deletion affecting part of the ELN gene has been identified in the boy and his father. A diagnosis of supravalvular aortic stenosis （SVAS） could be made based on the molecular finding.

关 键 词：主动脉瓣上狭窄 弹力蛋白基因 拷贝数变异 

分 类 号：R72[医药卫生—儿科]