俄罗斯家族性左心室心肌致密化不全患者的基因图谱

Genetic landscape in Russian patients with familial left ventricular noncompaction.

作者信息

Meshkov Alexey N, Myasnikov Roman P, Kiseleva Anna V, Kulikova Olga V, Sotnikova Evgeniia A, Kudryavtseva Maria M, Zharikova Anastasia A, Koretskiy Sergey N, Mershina Elena A, Ramensky Vasily E, Zaicenoka Marija, Vyatkin Yuri V, Kharlap Maria S, Nikityuk Tatiana G, Sinitsyn Valentin E, Divashuk Mikhail G, Kutsenko Vladimir A, Basargina Elena N, Barskiy Vladimir I, Sdvigova Nataliya A, Skirko Olga P, Efimova Irina A, Pokrovskaya Maria S, Drapkina Oxana M

机构信息

National Medical Research Center for Therapy and Preventive Medicine of the Ministry of Healthcare of the Russian Federation, Moscow, Russia.

National Medical Research Center for Cardiology of the Ministry of Healthcare of the Russian Federation, Moscow, Russia.

出版信息

Front Cardiovasc Med. 2023 May 24;10:1205787. doi: 10.3389/fcvm.2023.1205787. eCollection 2023.

DOI:10.3389/fcvm.2023.1205787

PMID:37342443

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10278580/

Abstract

BACKGROUND

Left ventricular noncompaction (LVNC) cardiomyopathy is a disorder that can be complicated by heart failure, arrhythmias, thromboembolism, and sudden cardiac death. The aim of this study is to clarify the genetic landscape of LVNC in a large cohort of well-phenotyped Russian patients with LVNC, including 48 families (n=214).

METHODS

All index patients underwent clinical examination and genetic analysis, as well as family members who agreed to participate in the clinical study and/or in the genetic testing. The genetic testing included next generation sequencing and genetic classification according to ACMG guidelines.

RESULTS

A total of 55 alleles of 54 pathogenic and likely pathogenic variants in 24 genes were identified, with the largest number in the MYH7 and TTN genes. A significant proportion of variants -8 of 54 (14.8%) -have not been described earlier in other populations and may be specific to LVNC patients in Russia. In LVNC patients, the presence of each subsequent variant is associated with increased odds of having more severe LVNC subtypes than isolated LVNC with preserved ejection fraction. The corresponding odds ratio is 2.77 (1.37 -7.37; p <0.001) per variant after adjustment for sex, age, and family.

CONCLUSION

Overall, the genetic analysis of LVNC patients, accompanied by cardiomyopathy-related family history analysis, resulted in a high diagnostic yield of 89.6%. These results suggest that genetic screening should be applied to the diagnosis and prognosis of LVNC patients.

摘要

背景

左心室心肌致密化不全（LVNC）心肌病是一种可并发心力衰竭、心律失常、血栓栓塞和心源性猝死的疾病。本研究的目的是阐明一大群具有明确表型的俄罗斯LVNC患者（包括48个家系，共214例）的LVNC遗传图谱。

方法

所有先证者均接受了临床检查和基因分析，同意参与临床研究和/或基因检测的家庭成员也接受了相关检查。基因检测包括下一代测序以及根据美国医学遗传学与基因组学学会（ACMG）指南进行基因分类。

结果

共鉴定出24个基因中的54个致病和可能致病变异的55个等位基因，其中MYH7和TTN基因中的数量最多。相当一部分变异——54个中的8个（14.8%）——此前在其他人群中未被描述，可能是俄罗斯LVNC患者所特有的。在LVNC患者中，每出现一个后续变异，与患有比单纯射血分数保留的LVNC更严重的LVNC亚型的几率增加相关。在对性别、年龄和家系进行校正后，每个变异的相应优势比为2.77（1.37 - 7.37；p <0.001）。