85例中国人长QT综合征先证者的临床特征及有关基因突变研究现状

Clinical characteristics of 85 probands with long QT syndrome and an update of genetic study in China

目的 研究我国长QT综合征 (LQTS)病人的临床特征和基因突变特点。方法 按照 1993年Schwartz等提出的LQTS诊断标准确诊为本病的家系 85个 ,分别来自 18个省、市、自治区。其中 4 3个家系由中国离子通道病注册中心的协作成员提供 ,其余为北京大学人民医院的LQTS随访患者。对先证者及其家族成员进行 6导联或 12导联心电图同步记录 ,对先证者的临床情况进行综合分析。对先证者及其家庭成员抽取外周血标本 ,用PCR SSCP加测序验证或经心电图初步分型后再进行PCR SSCP及测序的方法进行基因筛查。结果 先证者平均发病年龄 (17 3± 14 2 )岁 ,在 2 0岁以前发病的占 6 0 % ;女性居多 ,男性占 2 4 % ,女性占 76 %。发病症状有晕厥 (91 8% )、黑(2 8 9% )、心悸 (2 5 0 % )、胸闷 (34 2 % )及其它如抽搐、胸背痛、头晕 (2 1 1% )等 ;诱发因素有情绪紧张或激动 (5 1 3% ) ,劳累、运动或体力劳动 (5 1 3% ) ,休息或睡眠 (2 6 3% ) ,突然惊吓 /电话铃响 (19 7% ) ,经期或产褥期 (15 8% ) ,其它如寒冷或发烧 (15 8% )。病人的QTc值为 (0 .5 6±0 .0 7)s。LQTS病人的心电图上T波多变 ,QT间期可出现暂时正常化。有猝死家族史的家系占31 6 %。有LQTS家族史的占 6 3%。在 85个LQTS先证者中 ,同时伴聋哑 1例 ,预激?

Objective To study the clinical manifestations and gene mutations of Chinese long QT syndrome (LQTS) patients.MethodsAccording to the criteria by Schwartz 1993, probands of 85 families from 18 provinces were diagnosed as LQTS. Among them the information about 43 patients was provided by the National Registry, and a definite diagnosis for others were confirmed in our center. Six or 12 lead ECG for the probands and their family members was recorded and clinical manifestations for all probands were analyzed. Gene mutations were screened in KCNQ1,KCNH2 and KCNE1 using PCR and sequence analysis. ResultsThe age distribution for the first attack of probands is 17.3±14.2, and 60% of patients had their first attack before the age of 20. The sex distribution (male∶female) is around 1∶3, and the most prominent symptom is syncope (91.8%). The triggers are emotional stress (51.3%), physical stress, exercise or overwork (51.3%), during sleep or rest (26.3%), sudden noise/arousal (19.7%), menses or puerperium(15.8%), others (cold or fever) (15.8%). The QTc for probands is (0.56±0.07)s. The T wave morphology is varied, and QT interval could become temporarily normal. The families with sudden death history make up 31.6% of total 85 families. The families with more than 2 LQTS patients make up 63%. Among 85 probands, 1 case accompanied by deaf-mute, 1 case by WPW, 2 cases by myocarditis, 2 cases by bundle branch block, 1 by temporary atrio-ventricular block and 2 by hypertention. The predictive genotypic results by ECG characteristics are LQT1 (29.4%), LQT2(57.6%), LQT3(3.5%), and unpredictable (9.4%). The pacemaker plus β-blocker are effective for 4 patients and ICD plus β-blocker are effective for 1 patient. Left cardiac sympathetic denervation (LCSD) was performed on 15 patients. The therapy with β-blockers was conducted on most of other patients. Seven KCNQ1, 5 KCNH2 and 1 KCNE1 mutations have been identified in Chinese LQTS patients. Coexpression of HERG-R863X with wild-type HERG showed reduced current densities through no trafficing to the cell surface. KCNQ1-L191P and KCNE1-G52R have a dominant negative effect on I Ks, which reduces the I Ks current amplitude. ConclusionThe general clinical manifestations for Chinese LQTS patients are consistent with that reported by investigators from other countries. The predictive genotype results by ECG characteristics suggested that the major genotype for Chinese LQTS patients might be LQT2.β-blockers are the first-line therapy for LQTS patients. LCSD, pacemaker and ICD implantation are the choices for β-blocker resistant patients. Genetic and electrophysiological tests have shown promising results, suggesting that Chinese LQTS patients may have their own specific mutation sites and pathophysiological mechanisms.