长QT综合征KCNH2基因S4区新移码突变L539fs／47的研究

A novel mutation of the KCNH2 gene in a family with congenital long QT syndrome

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。

Objective To perform mutation analysis in a family with long QT syndrome. Methods The medical record of the affected child and his parents were collected. The locus of gene associated with the long QT syndrome was mapped by linkage analysis. Mutation analysis was done by PCR-single strand conformation polymorphism （SSCP） and direct sequencing. Results A mutation （L539fs/47） and a SNP （L564L） were found in exon 7 of the KCNH2 gene of the proband. The mutation was from the father. Conclusion A novel mutation of L539fs/47 in the KCNH2 gene was identified in the LQTS family, which might be the disease-causing mutation for the family.