Objective To identify the mutation of human ether-a-go-go-related gene(hERG)and analyze the clinical characteristics of a Chinese family with long ST syndrome(LQTS).Methods The electrocardiogram and DNA samples were obtained from a Chinese LQTS family of 26 members.Genotype was performed with polymorphic short tandem repeat(STR)markers at the known LQT1,LQT2,and LQT3 loci.SSCP analysis was used to find aberrant conformers.hERG mutation was confirmed by cloning and sequencing.Results Three gene carriers were linked to chromosome 7q35-36,where the potassium channel gene hERG was encoded.A 19-base pair deletion was identified.The mutation was located at nucleotide position 1 619-1 637 between transmembrane domains S4 and S5.Furthermore,A1692G polymorphism was found both in the normal control and patients.Conclusion A novel 19 bp deletion mutation of hERG is identified in a Chinese family.All gene carriers are demonstrated to be typical LQT2 ECG phenotype.
Jiang-Fang Lian,Xiao-Yan Huang,Wei-Feng Xu,Xi Yang,Ying Wang,Di Li,Jian-Qing Zhou Li Huili Hospital,Medical School of Ningbo University,Ningbo 315041,China
Objective To diagnose 6 LQTS families by genetic analysis.Methods A total aof 6 LQTS pedigrees with 43 family members were brought together for genetic diagnosis by using short-sequence tandem-repeat(STR)markers or sequencing.Genomic DNA was extracted from blood samples by standard procedure.STR markers or KCNQ1,KCNH2 and SCN5A were amplified.The haplotype analysis for LQTS was performed.If the family got the negative haplotype analysis,the sequencing was performed.Results LQTS patients were always linkaged with the SCN5A gene in family 1.KCNH2 was linkaged with the disease in family 2 to 5.21 gene carriers were identified from these 5 families.A mutation(A561V-KCNH2)was only found in the proband of family 6 and an SNP(G1691A)was found in all the members of the family.Conclusion Genetic diagnosis can not only improve presymptomatic diagnosis,but also provide the basis for personal therapy and research on disease-causing mutations.
Jiang-fang Lian1,Chen Huang2,Xiao-yan Huang1,Ying Wang1,Shi-jun Ge1,Jian-qing Zhou1 1.The Li Huili Hospital,Medical School of Ningbo University,Ningbo 315041
目的对1个先天性长QT综合征家系进行分子遗传学分析。方法应用短串联重复序列（short tandem repeat，STR）连锁分析确定突变基因的位点，聚合酶链反应-单链构象多态性结合测序的方法筛选KCNH2基因的突变。结果先证者KCNH2基因在第7外显子存在19bp的缺失，位于KCNH2基因编码序列1619～1637之间，同时突变基因的下游存在1个A1692G（CTA→CTG，L564L）多态位点，引起L539fs／47移码突变。突变基因来源于父亲，其兄弟为致病基因的携带者但未出现临床症状。结论KCNH2基因的L539fs／47移码突变是新突变点，是引起本家系临床症状的原因。
