Background:Hypertrophic cardiomyopathy (HCM) is mainly caused by mutations in sarcomere genes. Regarding the clinical implications of genetic information, little is known about the lifelong clinical effect of sarcomere mutations in Japanese HCM patients.

Methods and Results:We studied 211 consecutive Japanese patients with HCM who had agreed to genetic testing between 2003 and 2013. Genetic analyses were performed by direct DNA sequencing in the 6 common sarcomere genes (MYH7,MYBPC3,TNNT2,TNNI3,TPM1,ACTC). Through variant filtering, 21 mutations were identified in 67 patients. After excluding 8 patients whose variants were determined as having uncertain significance, finally 203 patients (130 men, age at study entry: 61.8±14.1 years) were investigated for clinical presentation and course. At the time of study entry, patients with mutations were younger, had more frequent non-sustained ventricular tachycardia, had greater interventricular wall thickness, were more frequently in the dilated phase and less frequently had apical HCM. Through their lifetimes, a total of 98 HCM-related morbid events occurred in 72 patients. Survival analysis revealed that patients with sarcomere gene mutations experienced those morbid events significantly more frequently, and this tendency was more prominent for lethal arrhythmic events.

Conclusions:In our HCM cohort, patients with sarcomere gene mutations had poorer lifelong outcome. Genetic information is considered important for better management of HCM.

背景：肥厚型心肌病（HCM）主要由肌节基因突变引起。关于遗传信息的临床意义，对日本 HCM 患者中肌节突变的终生临床影响知之甚少。

方法和结果：我们研究了 211 名同意在 2003 年至 2013 年间接受基因检测的连续日本 HCM 患者。通过直接 DNA 测序对 6 个常见肌节基因（ MYH7、 MYBPC3、 TNNT2、 TNNI3、 TPM1、 ACTC）进行遗传分析。）。通过变异过滤，在 67 名患者中发现了 21 个突变。在排除了 8 名变异被确定为具有不确定意义的患者后，最后对 203 名患者（130 名男性，研究开始时的年龄：61.8±14.1 岁）进行了临床表现和病程调查。在进入研究时，突变患者更年轻，非持续性室性心动过速更频繁，室壁更厚，扩张期更频繁，心尖 HCM 更少发生。在他们的一生中，72 名患者共发生了 98 次 HCM 相关的病态事件。生存分析显示，肌节基因突变的患者更频繁地经历这些病态事件，这种趋势在致死性心律失常事件中更为突出。

结论：在我们的 HCM 队列中，肌节基因突变患者的终生结局较差。遗传信息被认为对于更好地管理 HCM 很重要。