Massive Parallel DNA Sequencing of Patients with Inherited Cardiomyopathies in Cyprus and Suggestion of Digenic or...

Area of Science:

• Cardiovascular Genetics
• Molecular Cardiology
• Genomic Medicine

Background:

• Inherited cardiomyopathies are a diverse group of genetic heart diseases.
• These conditions can lead to severe outcomes like heart failure and sudden cardiac death.
• Genetic variants in cardiomyocyte genes are primary causes.

Purpose of the Study:

• To investigate the genetic basis of inherited cardiomyopathies in Cyprus.
• To identify DNA variants associated with cardiac phenotypes in affected families.
• To establish a genetic baseline for precision cardiology in the region.

Main Methods:

• Massive parallel DNA sequencing using a 72-gene panel.
• Computational prediction, database analysis, and in-house filtering for variant pathogenicity.
• Sanger sequencing for variant validation and familial segregation testing.

Main Results:

• Identified 41 distinct variants across 26 genes in 25 families.
• Fifteen variants were previously reported (12 disease-causing, 3 probable disease-causing).
• Twenty-six novel variants were discovered; classified as 28% VUS, 19.5% likely pathogenic, and 12.2% pathogenic.

Conclusions:

• Genetic heterogeneity and multiple variants complicate molecular diagnosis of cardiomyopathies.
• This study provides the first systematic genetic characterization of inherited cardiac conditions in Cyprus.
• Findings support the development of genetic diagnostics and precision cardiology approaches.