Identification of variants in genes associated with hypertrophic cardiomyopathy in Mexican patients

Abstract

The objective of this work was to identify genetic variants in Mexican patients diagnosed with hypertrophic cardiomyopathy (HCM). According to world literature, the genes mainly involved are MHY7 and MYBPC3, although variants have been found in more than 50 genes related to heart disease and sudden death, and to our knowledge there are no studies in the Mexican population. These variants are reported and classified in the ClinVar (PubMed) database and only some of them are recognized in the Online Mendelian Information in Men (OMIM). The present study included 37 patients, with 14 sporadic cases and 6 familial cases, with a total of 21 index cases. Next-generation sequencing was performed on a predesigned panel of 168 genes associated with heart disease and sudden death. The sequencing analysis revealed twelve (57%) pathogenic or probably pathogenic variants, 9 of them were familial cases, managing to identify pathogenic variants in relatives without symptoms of the disease. At the molecular level, nine of the 12 variants (75%) were single nucleotide changes, 2 (17%) deletions, and 1 (8%) splice site alteration. The genes involved were MYH7 (25%), MYBPC3 (25%) and ACADVL, KCNE1, TNNI3, TPM1, SLC22A5, TNNT2 (8%). In conclusion; we found five variants that were not previously reported in public databases. It is important to follow up on the reclassification of variants, especially those of uncertain significance in patients with symptoms of the condition. All patients included in the study and their relatives received family genetic counseling.

A novel pathogenic variant in the carnitine transporter gene, SLC22A5, in association with metabolic carnitine deficiency and cardiomyopathy features

“…The authors concluded that carnitine supplementation conferred echocardiographic improvements for 6 out of 8 treated patients over periods of 3 months to 2 years. García-Vielma et al [ 28 ] sought to identify genetic variants related to hypertrophic cardiomyopathy in Mexican patients. The authors maintained that while most global research primarily pointed to genes like MHY7 and MYBPC3 , there was a dearth of data on other genes.…”

Mitochondrial dysfunction in the pathogenesis of hypertrophic cardiomyopathy

“…Мутации чаще всего обнаруживаются в белках -основных участниках актомиозиновой системы подвижности. До 75% случаев ГКМП, вызванных мутациями в генах саркомерных белков, приходится на MYH7 и MYBPC3, 40 и 35% соответственно [16][17][18]. Тяжёлая цепь β-миозина и миозин-связывающий белок, кодируемые генами MYH7 и MYBPC3, при участии Ca-зависимой АТФазы и за счёт гибкости миозиновой головки обеспечивают скольжение актиновых и миозиновых нитей относительно друг друга.…”