Open AccessLeft ventricular noncompaction associated with titin-truncating variants in the TTN gene
Author(s) -
Ю А Вахрушев,
Tatiana Vershinina,
П. А. Федотов,
А. А. Козырева,
A. A. Kiselev,
Ю. В. Фомичева,
Е. С. Васичкина,
Tatiana Pervunina,
Anna Kostareva
Publication year - 2020
Publication title -
rossijskij kardiologičeskij žurnal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.141
H-Index - 14
eISSN - 2618-7620
pISSN - 1560-4071
DOI - 10.15829/1560-4071-2020-4027
Subject(s) - left ventricular noncompaction , titin , sanger sequencing , medicine , exome sequencing , nonsense , nonsense mutation , genetics , genetic diagnosis , gene , dna sequencing , mutation , genetic variants , cardiomyopathy , genotype , biology , missense mutation , heart failure , sarcomere , myocyte
Aim. To study the association of genetic variants in the titin gene ( TTN ) with the development and clinical course of left ventricular noncompaction in different age groups. Materialandmethods. The article discusses three clinical cases of patients with left ventricular noncompaction who were treated at theAlmazovNationalMedicalResearchCenter. We performed a new-generation sequencing of 108 genes associated with cardiomyopathies, as well as whole exome sequencing and Sanger sequencing. Results. We identified genetic variants in the TTN gene leading to the synthesis of truncated protein: in the first two cases, the cause of noncompaction was a thirteen nucleotide deletion with a reading frame shift, in the second, a nonsense mutation. An algorithm for assessing the pathogenicity of the identified variants and a scheme of diagnostic genetic search are presented. Conclusion. Causal role of TTN -truncating variants in development of cardiomyopathies and, in particular, left ventricular noncompaction, requires a comprehensive clinical, segregation and bioinformatic analysis using international databases and the use of bioinformatics software.