Komissarova S M, Rineiska N M, Chakova N N, Niyazova S S
State Institution Republican Scientific and Practical Centre «Cardiology».
Institute of Genetics and Cytology of Belarus National Academy of Sciences.
Kardiologiia. 2020 Mar 18;60(4):137-145. doi: 10.18087/cardio.2020.4.n728.
Aim To study the clinical course of the mixed phenotype (hypertrophic cardiomyopathy, HCMP, and left ventricular noncompaction, LVNC); to determine its genetic causes; and to evaluate incidence of cardiovascular complications (CVC) during the follow-up period.Material and methods In screening of 286 patients with HCMP, 8 of them (2.8 %; median age, 41.5 years; 4 men and 4 women) from unrelated families were found to have the mixed phenotype (combination of HCMP and LVNC). For their 10 first-degree relatives, the most frequent phenotype was HCMP without LVNC; however, both isolated LVNC and the mixed phenotype were also observed. Criteria for HCMP and LVNC were confirmed by echocardiography and cardiac magnetic resonance imaging Genotyping was performed by high-throughput sequencing NGT using the TruSight Cardio Sequencing Panel kit.Results Probands with the HCMP+LVNC combination compared to first-degree relatives with isolated HCMP and LVNC were characterized by more pronounced left ventricular dysfunction (ejection fraction, 43.57±7.6 and 53.64±6.51 %, respectively; p<0.001), a higher risk of CVC, and a higher incidence of ventricular tachyarrhythmias (7.9 and 2.2 %, respectively; p<0.01). 11 mutations in 5 genes were found in 8 patients with the mixed phenotype. 72.7 % of mutations were in the MYH7 and MYBPC3 genes that encode the heavy chain of β-myosin and myosin-binding protein C, respectively; however, in some cases, replacements in other genes (DTNA, TGFB2) were also found.Conclusion The mixed phenotype (HCMP and LVNC) is associated with more severe clinical course of the disease and unfavorable CVC.
目的 研究肥厚型心肌病(HCMP)与左心室心肌致密化不全(LVNC)混合表型的临床病程;确定其遗传病因;并评估随访期间心血管并发症(CVC)的发生率。材料与方法 在对286例HCMP患者进行筛查时,发现其中8例(2.8%;中位年龄41.5岁;4名男性和4名女性)来自无血缘关系的家庭,具有混合表型(HCMP与LVNC的组合)。对于他们的10名一级亲属,最常见的表型是无LVNC的HCMP;然而,也观察到了孤立的LVNC和混合表型。HCMP和LVNC的诊断标准通过超声心动图和心脏磁共振成像得以确认。使用TruSight Cardio测序试剂盒通过高通量测序NGT进行基因分型。结果 与孤立的HCMP和LVNC一级亲属相比,HCMP+LVNC组合的先证者具有更明显的左心室功能障碍(射血分数分别为43.57±7.6%和53.64±6.51%;p<0.001)、更高的CVC风险以及更高的室性快速心律失常发生率(分别为7.9%和2.2%;p<0.01)。8例混合表型患者中发现了5个基因的11个突变。72.7%的突变分别位于编码β-肌球蛋白重链和肌球蛋白结合蛋白C的MYH7和MYBPC3基因中;然而,在某些情况下,也发现了其他基因(DTNA、TGFB2)的替换。结论 混合表型(HCMP和LVNC)与更严重的疾病临床病程和不良的CVC相关。