致心律失常性右室心肌病DSP基因突变与表现型的关系

Clinical Feature and Profile of Desmoplakin Gene Mutation in Arrhythmogenic Right Ventricular Cardiomyopathy

【目的】在ARVC患者中筛选DSP基因突变,并与患者的表现型进行对比分析。【方法】收集ARVC患者40例,评估患者的临床指标,并随访心脏事件(室性心律失常、心衰和猝死)的发生。对其中32例ARVC患者的DSP基因突变进行筛选。【结果】患者出现症状的时间为32.2±12.7岁,男性患者的比例较高(85.0%),最常见的症状是心悸(82.5%),其次是胸痛(25.0%)和晕厥(22.5%)。T波倒置(75.0%)是最常见的心电图表现,随后QRS波时限延长(45.0%)和Epsilon波(35.0%)。伴左束支传导阻滞的室性心动过速有28例(70.0%)。32例ARVC患者中共7例(21.9%)患者发现了DSP突变,共检测出6个突变位点,对照组染色体(n=200)上并未发现这几个位点有改变。比较DSP和非DSP突变患者的临床特征,结果发现右室与左室容积之比两组之间的比较有意义(1.33±0.24 vs.1.28±0.14,P<0.05)。研究期间,共有3例患者死亡,平均死亡率是7.5%,DSP突变组有1例死亡,而非DSP突变组有2例死亡患者死亡。比较两组的生存时间无差别(19.43±2.38 vs.28.65±0.90,P>0.05)。【结论】DSP基因突变的检出率为21.9%,与国外的研究结果基本一致,但中国DSP突变患者的右室扩大较为明显,左室累及较少。

[ Objective ] The purpose of this study was to evaluate the long-term clinical outcomes and genetics of ARVC in China. [Methods] Forty subjects fulfilling modified task force criteria were included. Information on clinical presentation, electrocardiographic and cardiac imaging findings, and outcome of cases were underwent investigation. Genomic DNA was screened for mutations in DSP gene. [Results] The mean age at onset of symptoms （32.2 ± 12.7 years） and male predominance （85.0%） were similar to that reported in other studies. Palpitations were the most frequent symptom （82.5%）, followed by syncope （22.5%）. T-wave inversion was the most common presenting abnormality on resting 12-lead ECG （75%）, followed by localized QRS prolongation （45%） and epsilon waves （35%）. Ventricular taehyeardia with left bundle branch block morphology was subsequently documented in a total of 28 （70%） subjects during a study period. The cumulative mortality rate was 7.5%. Six DSP gene mutations were found in 7/ 32 （21.9%） unrelated participants, three being novel. Compound heterozygotes exhibited a severe phenotype in three patients. The right ventricular volume and left ventricular volume ratio （RV/LV ratio） was significant increased in the patients with DSP mutation compared to other ARVC patients （ 1.33 ± 0.24 vs 1.28 ± 0.14, P 〈 0.05）. Survival time in patients with DSP mutation was similar to other ARVC patients. [ Conclusion ] ARVC is associated with early mortality that is different to other countries population. Patients with DSP gene mutation have lager RV/LV ratio.