1 . 2018

Molecular genetic testing of the TTN gene in children with dilated cardiomyopathy

Abstract

The prevalence of dilated cardiomyopathy (DCM) is about 1:250 in population. The incidence of the newly diagnosed pediatric cases is 0.57 per 100,000 children annually. Genetic counseling for the families should be focused on verification of the genetic diagnosis, recurrence risk definition, and availability of the presymptomatic (including prenatal) diagnostics and preimplantation genetic testing for particular family.

According to various studies, mutations in the TTN gene accounts 10–30% of cases of idiopathic DCM. But these studies were mainly focused on the adult or mixed age groups of DCM patients. The frequency of mutations in the TTN gene, clinical manifestations and prognostic significance of the mutations in pediatric DCM cohort were not studied.

Aim – to determine mutation rate in the TTN gene in children with dilated cardiomyopathy, and estimate the relevance of mutational screening of this gene in pediatric DCM cohort.

Materal and methods. Complete clinical and instrumental examination of 25 pediatric DCM patients with DCM was performed in expert cardiology departments.

Molecular genetic study had included the semiconductor sequencing based on the IonTorrentTM platform of the coding and adjacent regulatory areas of the main cardiac isoform N2BA of the TTN gene (for 20 isolated cases); and whole exome sequencing trios on the Illumina platform (for 5 family cases).

Results and discussion. The group included 25 probands diagnosed with DCM before the age of 17 (the average age of diagnosis – 6.5 years). The gender ratio (M:F) was 17:7. Sporadic cases of DCM were 20, family cases – 5 (when DCM was diagnosed in at least one parent and/or sibling). Surprisingly, no mutation leading to the premature stop codon, or any other potentially pathogenic substitutions were found. Apparently TTN-related DCM manifests later in life, at least older than 18 years old.

Conclusion. The result of this study does not allow to consider the TTN gene as the first line of DNA diagnostics for DCM in the pediatric group, despite the publication of a high incidence of mutations in this gene in whole DCM cohort. Further studies are needed to compare the rate of the TTN gene mutations in DCM patients manifesting in different age.

Keywords:dilated cardiomyopathy, TTN, heart failure in children, primary cardiomyopathies, next generation sequencing

Clin. Experiment. Surg. Petrovsky J. 2018; 1 (19): 70–6.

DOI: 10.24411/2308-1198-2018-00010

Received: 15.01.2018. Accepted: 25.01.2018.

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