肥厚型心肌病心电图表型与MYH7-H1717Q、MYLK2-K324E和KCNQ1-R190W基因突变的关系初探

Relationship between electrocardiographic and genetic mutation （ MYH7-H1717Q, MYLK2-K324E and KCNQ1-R190W） phenotype in patients with hypertrophic cardiomyopathy

目的初探肥厚型心肌病一家系心电图表型与基因型的关系，观察肥厚型心肌病致病基因携带者早期的心电图改变。方法入选基因型明确的肥厚型心肌病一家系，3代共8名家庭成员，男性4例，女性4例。收集入选成员的临床资料，2次不同时间点12导联心电图、超声心动图等资料。分析家系成员的临床特点、心电图表型与基因型的关系。结果发现该家系成员共携带4种错义基因突变，分别为MYH7-H1717Q、MYLK2-K324E、KCNQ1-R190W和TMEM70-I147T。先证者携带全部4种基因突变，另有5名成员各携带2种突变。KCNQ1-H1717Q基因突变携带者校正QT间期（QTc）均显著延长，符合长QT综合征的心电图表现。MYLK2-K324E和KCNQ1-R190W基因突变携带者心电图表现为前侧壁或下壁导联可见q波和（或）ST段压低，T波低平、倒置。家系中携带致病基因，但超声心动图检查未发现心肌肥厚的成员，心电图表现为ST段压低，T波低平、倒置。仅带有TMEM70-I147T1个突变的携带者的心电图和超声心动图检查均未见异常。结论心脏离子通道和肥厚型心肌病相关致病基因的联合突变与肥厚型心肌病患者的心电图表型有关系。肥厚型心肌病致病基因携带者的心电图改变可早于超声心动图改变和临床症状。心电图异常或可作为肥厚型心肌病致病基因携带者进展成肥厚型心肌病的早期预警筛查指标之一。

Objective To explore the relationship between electrocardiographic （ECG） and genetic mutations of patients with hypertrophic eardiomyopathy （ HCM ） , and early ECG changes in HCM patients. Methods Clinical, 12-lead ECG and ecbocardiographic examination as well as genetic examinations were made in a three-generation Chinses HCM pedigree with 8 family members （4 males）. The clinical characterization and ECG parameters were analyzed and their relationship with genotypes in the family was explored. Results Four missense mutations （MYHT-H1717Q, MYLK2-K324E, KCNQ1- R190W, TMEMT0-I147T） were detected in this pedigree. The proband carried all 4 mutations and 5 members carried 2 mutations. Corrected QTc interval of KCNQ1-H1717Q carriers was significantly prolonged and was consistent with the ECG characterization of long QT syndrome. MYLK2-K324E and KCNQ1 -R190W carriers presented with Q wave and （or） depressed ST segment, as well as flatted or reversed T waves in leads from anterolateral and inferior ventricular walls. ECG results showed ST segment depression, flat and inverted T wave in the gene mutation carriers with normal echocardiographic examination results. ECG and echocardiographie results were normal in TMEM70-I147T mutation carrier. Conclusions The combined mutations of the genes associated with cardiac ion channels and HCM are linked with the ECG phenotype changes in this HCM pedigree. The variations in ECG parameters due to the genetic mutation appear earlier than the echocardiography and clinical manifestations. Variation in ECG may become one of the indexes for early diagnostic screening and disease progression of the HCM gene mutation carriers.