Work

Novel combination of TTN and CTNNA3 Pathogenic variant leading to Familial Dilated Cardiomyopathy: From acute heart failure to subclinical phenotypes.

Year: 2025

Type: article

Abstract: Background Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure and the most common indication for cardiac transplantation in young adults. The clinical spectrum of DCM is heterogeneous, ranging from asymptomatic left ventricular dysfunction to advanced heart failure, arrhythmias, and sudden cardiac death. Methods Whole-exome sequencing (WES) was performed on germline DNA of the index case followed by segregation analysis of the identified variants on family ‘members by Sanger sequencing. Results We identified in the proband, a boy aged of 2-years, heterozygous germline nonsense variant in the TTN gene (c.95008C>T, p.Arg31670*), combined with other nonsense variant in the CTNNA3 gene (c.2023G>T, p.Glu675*). Segregation analysis revealed that both variants co-segregate with the disease phenotype within the family. This is the first report of the co-occurrence of pathogenic/likely pathogenic nonsense variants in TTN and CTNNA3 genes in DCM patients. Conclusions Our findings expand the mutational spectrum of DCM in North African populations and underscore the importance of genetic screening in familial cardiomyopathies.

Source: F1000Research

DOI: 10.12688/f1000research.170824.1