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Identification of a novel likely pathogenic TPM1 variant linked to hypertrophic cardiomyopathy in a family with sudden cardiac death.
- 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&#95;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.)
- Subjects :
- Humans
Male
Female
Adult
Middle Aged
Exome Sequencing
Magnetic Resonance Imaging, Cine methods
Echocardiography
Phenotype
Electrocardiography
Iran epidemiology
Mutation, Missense
DNA genetics
Tropomyosin genetics
Death, Sudden, Cardiac etiology
Pedigree
Cardiomyopathy, Hypertrophic genetics
Cardiomyopathy, Hypertrophic complications
Cardiomyopathy, Hypertrophic diagnosis
Subjects
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