Identification of a rare variant in TNNT3 responsible for familial dilated cardiomyopathy through whole-exome sequencing and in silico analysis.

ABSTRACT:

Background

Dilated cardiomyopathy (DCM) is a prevalent etiology of heart failure, distinguished by the gradual and frequently irreversible myocardial muscle impairment. Roughly 50% of DCM occurrences stem from hereditary rare variants. In this study, our aim was to identify the genetic cause of DCM in a pedigree with several affected individuals across four generations.

Methods

Whole exome sequencing was performed on the proband, with variants filtered and analyzed using in silico tools. Co-segregation analysis was conducted using Sanger sequencing. Protein structure modeling and protein-protein interaction evaluations were performed using AlphaFold3 and HADDOCK2.4, respectively.

Results

We identified a missense rare variant in the TNNT3 gene, leading to the p.Glu125G

SUBMITTER: Jadidi M 

PROVIDER: S-EPMC12117963 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature