A Case Series of Hypertrophic Cardiomyopathy Conducted in Vietnam Revealing a Novel Pathogenic Variant of the TNNT2 Gene

Abstract

Background: Hypertrophic Cardiomyopathy (HCM) is one of the leading causes of sudden cardiac death in adults.HCM is inherited in an autosomal dominant manner; however, the genetic etiology of the disease is not fully explained and studies on the hereditary characteristics in family trees are still underway. Methods: Ten HCM patients and 31 of their relatives were recruited. Targeted sequencing for 4 HCM related-genes, including MYH7, MYBPC3, TNNT2, and TNNI3, using targeted next-generation sequencing (NGS) was carried out. Demographic, clinical, electrocardiography, and echocardiography characteristics were also characterized. Results: Among the 10 HCM patients, 5 were identified with the HCM pathogenic variants in MYH7 (3 patients), MYBPC3 (1 patient), and TNNT2 (1 patient) genes. Eleven out of 31 relatives from these 5 genotype-positive patients carried the same pathogenic variants. We found the novel c.822-2 A>G variant in the splicing site of the TNNT2 gene responsible for HCM disease in a family with 7 subjects genotype positive and 3 others who suffered from sudden cardiac death. Conclusion: This case series highlighted the importance of genetic testing for clinically confirmed HCM patients and family members. The genetic information can be used as a molecular marker to complement the clinical presentation in the diagnosis of HCM, as well as a prognostic tool for the patients and their family members.