Whole-exome sequencing identified a likely pathogenic heterozygous missense variant in the TNNT2 gene (c.311G > A, p.Arg104His) in a 41-year-old Chinese male with sporadic dilated cardiomyopathy.
Case Report (n=1)
No
The identification of the TNNT2 c.311G > A (p.Arg104His) variant in a sporadic DCM case underscores the importance of genetic testing and expands the known phenotypic spectrum of TNNT2 variants.
Purpose This study aims to characterize the clinical and genetic features of a sporadic case of dilated cardiomyopathy (DCM) associated with a TNNT2 variant and to review the variant spectrum of the TNNT2 gene in the Chinese DCM population. Patients and methods A 41-year-old male proband diagnosed with DCM underwent comprehensive clinical evaluation. Whole-exome sequencing (WES) was performed on the proband to identify potential causative variants. Subsequently, Sanger sequencing was used to specifically validate the candidate TNNT2 variant in the proband and all available family members. Bioinformatic tools were employed to predict the pathogenicity of the identified variant, which was interpreted according to the American College of Medical Genetics and Genomics (ACMG) guidelines. A literature review of TNNT2 variants in Chinese DCM patients was conducted. Results Clinical assessment revealed left ventricular dilation and systolic dysfunction in the proband. Genetic analysis identified a heterozygous missense variant in the TNNT2 gene (c.311G A, p.Arg104His). Bioinformatic predictions consistently supported its deleterious effect and high conservation. The variant was not found in the available family members. Considering the maternal sudden death history, it is likely to be de novo or maternally inherited. Based on ACMG guidelines, the variant was classified as “Likely Pathogenic”. The literature review summarized 14 distinct TNNT2 variants from 20 reported Chinese DCM cases. Conclusion This study provides a detailed clinical characterization of the TNNT2 c.311G A (p.Arg104His) variant in a Chinese patient with sporadic DCM, contributing to the understanding of its phenotypic spectrum. The review provides an overview of the TNNT2 variant spectrum in the Chinese DCM population.
Chen et al. (Thu,) conducted a case report in Dilated cardiomyopathy (n=1). Whole-exome sequencing was evaluated on Identification of causative genetic variant. Whole-exome sequencing identified a likely pathogenic heterozygous missense variant in the TNNT2 gene (c.311G > A, p.Arg104His) in a 41-year-old Chinese male with sporadic dilated cardiomyopathy.