6个长QT综合征家系的分子遗传学检测  

Long QT syndrome diagnosed by genetic analysis in six pedigress

作　　者：廉姜芳[1] 黄辰[2] 崔长琮[2] 薛小临[2] 

机构地区：[1]宁波市医疗中心李惠利医院心内科,浙江宁波315042 [2]西安交通大学环境与疾病相关基因教育部重点实验室

出　　处：《中国心脏起搏与心电生理杂志》2006年第1期18-20,共3页Chinese Journal of Cardiac Pacing and Electrophysiology

基　　金：陕西省自然科学基金资助(2003C210);中国自然科学基金资助(39760323和3100067);宁波市青年博士基金(2005A610016)

摘　　要：目的 对6个先天性长QT综合征（long QT syndrome，LQTS）家系成员进行基因检测。方法 运用位于KCNH2和SCN5A基因内和临近的短串联重复（short tandem repeat，STR）（D7S1824、D7S2493、D7S483、D3S1298、D3S1767、D3S3521）位点确定染色体单体型。6个家系的所有成员进行单倍型连锁分析，确定基因型。1个家系经直接测序确定其基因型。结果 家系1的致病基因位于染色体LQT3位点，而家系2—6的致病基因位于LQT2位点，家系6经直接测序确定该家系的先证者为散发病例，突变基因为KCNH2。确诊LQTS患者22例，其中6例为无症状基因携带者，排除6例可疑患者。结论 LQTS的遗传学研究检测不但能确定LQTS基因分型，而且可进行LQTS的症状前诊断。从而为临床的基因靶向治疗提供依据。Objective Long QT syndrome （LQTS） is a monogenic disorder that produces cardiac arrhythmias and can lead to sudden death. 6 LQTS pedigree with 43 family members were used together for genetic diagnosis. Methods Genetic studies were performed by using short-sequence tandem-repeat （STR） markers or sequencing. Genomic DNA was extracted from blood samples by standard procedure. STR markers （D7S1824, D7S2439, D7S483, D3S1298, D3S1767, D3S3521 ） in or spanning the KCNH2 and SCN5A were amplified, the haplotype analysis for LQTS was performed, if the family were the negative in haplotype analysis, the sequencing was performed. Results LQTS patients were always linkaged with the SCN5A gene in family 1, KCNH2 was linkage with the disease in family 2 to 5. 21 gene carriers were identified from these 5 families. A mutation （A561V） in No. 7 exon of KCNH2 gene was only found in the proband of family 6 and a SNP （G1691A） was found in all members of the family. Conclusions Genetic diagnosis not only improve presymptomatic diagnosis, but also provide the base for different drug for different gene carriers.

关 键 词：心血管病学 先天性长QT综合征 短串联重复序列 连锁分析 测序 

分 类 号：R541.7[医药卫生—心血管疾病]