先天性长QT综合征KVLQT1和HERG基因新突变位点的检测

目的：研究中国人先天性长QT综合征（long QT syndrome,LQTS)HERG和KVLQT1的基因突变情况。方法，利用聚合酶链反应和DNA测序对11个LQTS家系HERG跨膜编码区S1－S6和KVLQT1跨膜编码区S2－S6进行基因检测。结果（1）11个LQTS患者在国外已知突变点均无突变；（2）发现4个新的错义突变位点，分别为T1515G（HERG），C682T，C934T，G983A（KVLQT1）。其对应的氨基酸改变为E505D，R228C，S230L，P312S和R328C。结论：在中国人LQTS患者HERG和KVLQT1上发现了4个新的基因突变位点。

The novel HERG and KVLQT1 mutations in Chinese familial long QT syndrome

Objective Familial long QT syndrome (LQLS)is an inherited cardiac disorder that results in syn- cope, seizures, and sudden death in young, healthy people. Five genes have been implicated in LQTS: KVLQT1, HERG, SCN5A, KCNE1, KCNE2. KVLQT1, HERG, KCNE1 and KCNE2 encode potassium channel subunits and the cardiac sodium channel gene is encoded by SCN5A gene. A serial of mutations about these five genes have been reported in some countries kindreds. We investigated mutation of KVLQT1, HERG gene in Chinese LQT fami- lies. Methods Eleven Chinese families with LQTS were brought together for screening for KVLQT1, HERG gene mutation. Genomic DNA from each proband was examined by the polymerase chain reaction (PCR) technique followed by direct DNA sequencing. Results Four mutations were found. One mutation of HERG is T1515G (E505D), the others of KVLQT1 were C682T (R228C), C934T (P312S), G983A (R328C). These mutations was present in af- fected family members, and was not present in unaffected family members or in 100 unrelated normal individuals. Conclusion We presumed these mutations are associated with LQTS, because they segrgate with disease and were not found in normal individuals. The mutations may result in reducing IK channel, thereby leading to LQTS. Genetic heterogeneity in Chinese LQT families may be exist.