Genetic landscape in Russian patients with familial left ventricular noncompaction

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

doi:10.3389/fcvm.2023.1205787

Genetic landscape in Russian patients with familial left ventricular noncompaction

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

Authors

Alexey N Meshkov^#^{1

2

3

4}, Roman P Myasnikov^#¹, Anna V Kiseleva^#¹, Olga V Kulikova^#¹, Evgeniia A Sotnikova¹, Maria M Kudryavtseva¹, Anastasia A Zharikova^{1

5}, Sergey N Koretskiy¹, Elena A Mershina⁶, Vasily E Ramensky^{1

5}, Marija Zaicenoka⁷, Yuri V Vyatkin^{1

8}, Maria S Kharlap¹, Tatiana G Nikityuk¹, Valentin E Sinitsyn⁶, Mikhail G Divashuk^{1

9}, Vladimir A Kutsenko^{1

10}, Elena N Basargina¹¹, Vladimir I Barskiy¹¹, Nataliya A Sdvigova¹¹, Olga P Skirko¹, Irina A Efimova¹, Maria S Pokrovskaya¹, Oxana M Drapkina¹

Affiliations

¹ National Medical Research Center for Therapy and Preventive Medicine of the Ministry of Healthcare of the Russian Federation, Moscow, Russia.
² National Medical Research Center for Cardiology of the Ministry of Healthcare of the Russian Federation, Moscow, Russia.
³ Hereditary Metabolic Diseases Laboratory, Research Centre for Medical Genetics, Moscow, Russia.
⁴ Department of General and Medical Genetics, Pirogov Russian National Research Medical University, Moscow, Russia.
⁵ Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia.
⁶ Medical Research and Educational Center, Lomonosov Moscow State University, Moscow, Russia.
⁷ Phystech School of Biological and Medical Physics, Moscow Institute of Physics and Technology, Dolgoprudny, Russia.
⁸ Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia.
⁹ Laboratory of Applied Genomics and Crop Breeding, All-Russia Research Institute of Agricultural Biotechnology, Moscow, Russia.
¹⁰ Faculty of Mechanics and Mathematics, Lomonosov Moscow State University, Moscow, Russia.
¹¹ National Medical Research Center for Children's Health, Moscow, Russia.

^# Contributed equally.

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.

Keywords: LVNC; MYH7; TTN; family form; genetic screening; left ventricular noncompaction cardiomyopathy.

© 2023 Meshkov, Myasnikov, Kiseleva, Kulikova, Sotnikova, Kudryavtseva, Zharikova, Koretskiy, Mershina, Ramensky, Zaicenoka, Vyatkin, Kharlap, Nikityuk, Sinitsyn, Divashuk, Kutsenko, Basargina, Barskiy, Sdvigova, Skirko, Efimova, Pokrovskaya and Drapkina.