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Features of the appearance of clinical cardiomyopathies against the background of truncating variants in the ttn gene: a review of the literature and an analysis of the appearance.

https://doi.org/10.18705/2311-4495-2023-10-5-430-448

EDN: KDPSIU

Abstract

Background. To date, the influence of genetic variants in the titin gene on the development of all types of cardiomyopathies has been proven, and this primarily applies to TTNtv, however, the high frequency of these variants in the control population (1–3 %) significantly complicates the determination of the pathogenicity of the detected variants. In addition, due to a significant population frequency (1–3 %) in patients with CMP, variants in the titin gene are often combined with causal variants in other genes, and thus can act as modifiers of the clinical course of the disease and myocardial remodeling.

Objective. To study the effect of shortening variants in the titin gene on the clinical course of cardiomyopathies in the presence of causative variants in other genes or etiological factors of the disease.

Design and methods. This article will consider three clinical cases of patients diagnosed with CMP who were treated at the Almazov National Medical Research Center. To conduct a genetic examination, next generation sequencing was used with a target cardiopanel to check 108 genes associated with the development of cardiomyopathies, as well as Sanger sequencing to exclude false positive results.

Results. During a genetic examination of the studied patients, identified genetic variants in the titin gene led to the syn- thesis of a truncated protein: in all cases, the reason for this was frameshift deletions located in exons with a PSI (Percent Spliced-In) level of 100%. According to the American College of Medical Genetics and Genomics pathogenicity classification, two genetic variants are classified as pathogenic and one is classified as probably pathogenic.

Conclusion. In these patients, we found shortening variants (frameshift deletions) in the titin gene, which acted as modifiers of myocardial remodeling.

About the Authors

Yu. A. Vakhrushev
Almazov National Medical Research Centre
Russian Federation

Yuri A. Vakhrushev, Assistant at the Department of
Clinical Laboratory Diagnostics and Genetics

Akkuratova str., 2, Saint Petersburg, 197341



S. Ye. Andreeva
Almazov National Medical Research Centre
Russian Federation

Sofia Ye. Andreeva, Research Laboratory Assistant at
the World-Class Research Centre for Personalized Medicine of the Almazov National Medical Research Centre, firstyear doctoral student at the Department of Cardiology

Akkuratova str., 2, Saint Petersburg, 197341



A. Ya Gudkova
Almazov National Medical Research Centre
Russian Federation

Alexandra Ya. Gudkova, D.M.Sc., Professor, Head
of the Cardiomyopathies Laboratory at the Institute of
Cardiovascular Diseases

Akkuratova str., 2, Saint Petersburg, 197341



T. S. Kovalchuk
Almazov National Medical Research Centre
Russian Federation

Tatiana S. Kovalchuk, Unior Researcher at the Research
Laboratory of Pediatric Arrhythmology, Pediatrician, Pediatric Cardiologist

Akkuratova str., 2, Saint Petersburg, 197341



D. Yu. Alekseeva
Almazov National Medical Research Centre
Russian Federation

Daria Yu. Alekseeva, MD, Researcher at the Research
Laboratory of Electrocardiology

Akkuratova str., 2, Saint Petersburg, 197341



A. A. Khodot
Almazov National Medical Research Centre
Russian Federation

Anna A. Khodot, Laboratory Assistant at the Department
of Faculty Therapy with Clinic

Akkuratova str., 2, Saint Petersburg, 197341



E. S. Vasichkina
Almazov National Medical Research Centre
Russian Federation

Elena S. Vasichkina, D.M.Sc., Chief Researcher at the
Research Institute of Pediatric Cardiovascular Diseases

Akkuratova str., 2, Saint Petersburg, 197341



O. O. Yaznevich
Almazov National Medical Research Centre
Russian Federation

Oksana O. Yaznevich, Second Qualification Category
Cardiologist in the Cardiology Department No. 8

Akkuratova str., 2, Saint Petersburg, 197341



M. A. Bortcova
Almazov National Medical Research Centre
Russian Federation

Maria A. Bortcova, Head of the Cardiology Department
No. 8, Senior, Cardiologist

Akkuratova str., 2, Saint Petersburg, 197341



A. A. Kostareva
Almazov National Medical Research Centre
Russian Federation

Anna A. Kostareva, D.M.Sc., Director of the Institute
of Molecular Biology and Genetics

Akkuratova str., 2, Saint Petersburg, 197341



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Review

For citations:


Vakhrushev Yu.A., Andreeva S.Ye., Gudkova A.Ya., Kovalchuk T.S., Alekseeva D.Yu., Khodot A.A., Vasichkina E.S., Yaznevich O.O., Bortcova M.A., Kostareva A.A. Features of the appearance of clinical cardiomyopathies against the background of truncating variants in the ttn gene: a review of the literature and an analysis of the appearance. Translational Medicine. 2023;10(5):430-448. (In Russ.) https://doi.org/10.18705/2311-4495-2023-10-5-430-448. EDN: KDPSIU

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ISSN 2311-4495 (Print)
ISSN 2410-5155 (Online)