6个长QT综合征家系的分子遗传学检测

目的对6个先天性长QT综合征(long QT syndrom e,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。

Long QT syndrome diagnosed by genetic analysis in six pedigress

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.Chinese Journal of Cardiac Pacing and Electrophysiology,2006,20(1):18~ 20]