THE NEW GENOME VARIANTS IN RUSSIAN CHILDREN WITH GENETICALLY DETERMINED CARDIOMYOPATHIES REVEALED WITH MASSIVE PARALLEL SEQUENCING

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Abstract


Background: Cardiomyopathies in children are serious, continuously progressing myocardium diseases which are characterized by a variety of the causes, symptoms, implications, and high lethality. More than 400 genes that can cause hereditary heart and vessels diseases are described in scientific literature. The application of a high-performance method of massive parallel sequencing allows to conduct the investigation of genome extended targeted areas revealing the variants and analyzing them (bioinformatics) for pathogenicity.

Aims: Identification of a genetic etiology of hereditary cardiomyopathies development in children’s population of the Russian Federation.

Materials and methods: The research included 103 patients with various phenotypes of cardiomyopathies aged from 3 months up to 17 years 9 months who at the moment of examination were observed in the cardiology department and the department of recovery treatment with cardiovascular diseases in the NMRCCH. All patients were performed massive parallel sequencing analyzing the targeted areas of 404 genes which mutations lead to the development of heart and vessels hereditary diseases.

Results: The diagnostic algorithm based on the method of a massive parallel sequencing was developed. 176 258 minor options were identified in the explored target areas of genome of 103 patients. An average number of the revealed nucleotide replacements different from the reference sequence was 1711. We observed that about 40% of all variants founded by our means were found in MYH7, MYBPC3, TTN, MYH6, SCN5A, DSC2 and TPM1 genes. Bioinformatics analysis allowed revealing 68 novel genome variants associated with cardiomyopathy development. The reliable association of carriage of pathogenic option in MYBPC3 gene with development of hypertrophic cardiomyopathy in the Russian children was found.

Conclusions: The application of the offered algorithm allowed establishing laboratory diagnoses to 99 (96.1%) patients out from 103 investigated subjects including the syndromal and non-syndromal forms of heart and vessels hereditary diseases which showed a cardiomyopathy phenotype.


K. V. Savostyanov

National Medical Research Center of Children's Health

Author for correspondence.
Email: 7443333@gmail.com
ORCID iD: 0000-0003-4885-4171

Russian Federation Moscow

L. S. Namazova-Baranova

National Medical Research Center of Children's Health

Email: namazova@nczd.ru
ORCID iD: 0000-0002-2209-7531

Russian Federation Moscow

E. N. Basargina

National Medical Research Center of Children's Health

Email: basargina@nczd.ru
ORCID iD: 0000-0002-0144-2885

Russian Federation Moscow

N. D. Vashakmadze

National Medical Research Center of Children's Health

Email: vashakmadze@nczd.ru
ORCID iD: 0000-0001-8320-2027

Russian Federation Moscow

N. V. Zhurkova

National Medical Research Center of Children's Health

Email: zhurkovanv@nczd.ru
ORCID iD: 0000-0001-6614-6115

Russian Federation Moscow

A. A. Pushkov

National Medical Research Center of Children's Health

Email: pushkovaa@nczd.ru
ORCID iD: 0000-0001-6648-2063

Russian Federation Moscow

I. S. Zhanin

National Medical Research Center of Children's Health

Email: ilya_zhanin@outlook.com
ORCID iD: 0000-0003-1423-0379

Russian Federation Moscow

N. А. Sdvigova

National Medical Research Center of Children's Health

Email: sdvigova-natalya@yandex.ru
ORCID iD: 0000-0002-5313-1237

Russian Federation Moscow

V. Yu. Lukanina

National Medical Research Center of Children's Health

Email: lukanina@nczd.ru
ORCID iD: 0000-0002-2133-8284

Russian Federation Moscow

A. Nikitin

National Medical Research Center of Children's Health

Email: avialn@gmail.com
ORCID iD: 0000-0001-9762-3383

Russian Federation Moscow

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