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Identification of a novel likely pathogenic TPM1 variant linked to hypertrophic cardiomyopathy in a family with sudden cardiac death.

Authors :
Azimi A
Soveizi M
Salmanipour A
Mozafarybazargany M
Ghaffari Jolfayi A
Maleki M
Kalayinia S
Source :
ESC heart failure [ESC Heart Fail] 2024 Oct; Vol. 11 (5), pp. 3180-3190. Date of Electronic Publication: 2024 Jun 14.
Publication Year :
2024

Abstract

Aims: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic cardiac disorder characterized by unexplained left ventricular hypertrophy. It can cause a wide spectrum of clinical manifestations, ranging from asymptomatic to heart failure and sudden cardiac death (SCD). Approximately half of HCM cases are caused by variants in sarcomeric proteins, including α-tropomyosin (TPM1). In this study, we aimed to characterize the clinical and molecular phenotype of HCM in an Iranian pedigree with SCD.<br />Methods and Results: The proband and available family members underwent comprehensive clinical evaluations, including echocardiography, cardiac magnetic resonance (CMR) imaging and electrocardiography (ECG). Whole-exome sequencing (WES) was performed in all available family members to identify the causal variant, which was validated, and segregation analysis was conducted via Sanger sequencing. WES identified a novel missense variant, c.761A>G:p.D254G (NM_001018005.2), in the TPM1 gene, in the proband, his father and one of his sisters. Bioinformatic analysis predicted it to be likely pathogenic. Clinical features in affected individuals were consistent with HCM.<br />Conclusions: The identification of a novel TPM1 variant in a family with HCM and SCD underscores the critical role of genetic screening in at-risk families. Early detection of pathogenic variants can facilitate timely intervention and management, potentially reducing the risk of SCD in individuals with HCM.<br /> (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Details

Language :
English
ISSN :
2055-5822
Volume :
11
Issue :
5
Database :
MEDLINE
Journal :
ESC heart failure
Publication Type :
Academic Journal
Accession number :
38874371
Full Text :
https://doi.org/10.1002/ehf2.14906