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Abstract：
Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disorder characterized by marked clinical and genetic heterogeneity. Ethnic groups underrepresented in studies may have distinctive characteristics. We sought to evaluate the clinical and genetic landscape of Russian HCM patients. A total of 193 patients (52% male; 95% Eastern Slavic origin; median age 56 years) were clinically evaluated, including genetic testing, and prospectively followed to document outcomes. As a result, 48% had obstructive HCM, 25% had HCM in family, 21% were asymptomatic, and 68% had comorbidities. During 2.8 years of follow-up, the all-cause mortality rate was 2.86%/year. A total of 5.7% received an implantable cardioverter-defibrillator (ICD), and 21% had septal reduction therapy. A sequencing analysis of 176 probands identified 64 causative variants in 66 patients (38%); recurrent variants were MYBPC3 p.Q1233* (8), MYBPC3 p.R346H (2), MYH7 p.A729P (2), TPM1 p.Q210R (3), and FLNC p.H1834Y (2); 10 were multiple variant carriers (5.7%); 5 had non-sarcomeric HCM, ALPK3, TRIM63, and FLNC. Thin filament variant carriers had a worse prognosis for heart failure (HR = 7.9, p = 0.007). In conclusion, in the Russian HCM population, the low use of ICD and relatively high mortality should be noted by clinicians; some distinct recurrent variants are suspected to have a founder effect; and family studies on some rare variants enriched worldwide knowledge in HCM.
摘要：
肥厚型心肌病（HCM）是一种常见的遗传性心脏病，具有明显的临床和遗传异质性。研究中代表性不足的族裔群体可能具有独特的特征。我们试图评估俄罗斯HCM患者的临床和遗传前景。对193例患者（52%为男性；95%为东部斯拉夫血统；中位年龄56岁）进行了临床评估，包括基因检测,并前瞻性地记录结果。因此,48%患有阻塞性HCM,25%的家庭有HCM，21%无症状，68%有合并症。在2.8年的随访中，全因死亡率为2.86%/年。总共5.7%的人接受了植入式心脏复律除颤器(ICD)，21%的患者接受了中隔缩小治疗。对176位先证者的测序分析在66位患者（38％）中鉴定出64位致病变异；复发变异为MYBPC3p.Q1233*（8），MYBPC3p.R346H(2),MYH7p.A729P(2),TPM1p.Q210R（3），和FLNCp.H1834Y（2）；10个是多变异携带者（5.7％）；5个患有非肌节HCM，ALPK3、TRIM63和FLNC。纤丝变异携带者对心力衰竭的预后较差（HR=7.9，p=0.007）。总之,在俄罗斯的HCM人口中，临床医师应注意ICD的低使用率和相对较高的死亡率;一些明显的复发变异被怀疑具有建立效应;对一些罕见变异的家庭研究丰富了HCM的全球知识.
