Three Novel Pathogenic Variants in Unrelated Vietnamese Patients with Cardiomyopathy

Area of Science:

• Cardiovascular Genetics
• Molecular Cardiology
• Genomic Medicine

Background:

• Cardiomyopathy, including dilated (DCM) and hypertrophic (HCM), is a major cause of heart failure and a leading reason for heart transplantation.
• Genetic factors account for 20-50% of cardiomyopathy cases, highlighting the need for genetic basis understanding.
• Genetic insights are crucial for disease pathogenesis, diagnosis, treatment, prevention, and family genetic counseling.

Purpose of the Study:

• To identify genetic variants associated with cardiomyopathy in Vietnamese patients.
• To understand the role of genetic mutations in the pathogenesis of cardiomyopathy.
• To provide a foundation for improved diagnosis, treatment, and genetic counseling for affected families.

Main Methods:

• Collected samples from nine patients from Vietnamese families diagnosed with cardiomyopathy.
• Performed whole-exome sequencing (WES) to detect genetic variants.
• Validated identified variants using Sanger sequencing and predicted their pathogenicity with in silico tools.

Main Results:

• Identified nine heterozygous variants causative of disease in the patients.
• Discovered three novel variants (in MYL2, MYH7, DES genes) and two pathogenic variants (in MYH7, PTPN11 genes).
• Found four variants of uncertain significance in ACTA2, ANK2, MYOZ2, and PRKAG2 genes; in silico analysis confirmed pathogenicity for DCM.

Conclusions:

• The study identified key genetic variants contributing to cardiomyopathy in Vietnamese patients.
• Findings enhance the understanding of cardiomyopathy pathogenesis.
• Results support improved genetic diagnosis, targeted treatments, preventative strategies, and family genetic counseling.