Hereditary Dilated Cardiomyopathy: Recent Advances in Genetic Diagnostics

Area of Science:

• Cardiovascular Genetics
• Molecular Cardiology
• Genomic Medicine

Background:

• Dilated cardiomyopathy (DCM) is a primary cause of heart failure in young adults.
• Genetic factors contribute significantly to idiopathic DCM, yet genetic testing accessibility remains a challenge due to complexity.
• Advancements in next-generation sequencing (NGS) have enabled multi-gene testing for DCM.

Purpose of the Study:

• To evaluate the diagnostic yield and spectrum of causative genes in Korean idiopathic DCM patients using NGS.
• To assess the prevalence of rare or novel variants in DCM candidate genes.
• To explore the utility of integrated clinical and genetic data for improved DCM diagnosis.

Main Methods:

• Targeted gene panel sequencing utilizing next-generation sequencing (NGS) technology.
• Analysis of genetic variants in a cohort of Korean patients with idiopathic DCM.
• Comparison of identified gene patterns with previous international reports.

Main Results:

• The NGS-based genetic testing achieved a diagnostic detection rate of approximately 40% in idiopathic DCM patients.
• MYBPC3, LMNA, and MYH7 were the most frequently identified causative genes, with a distinct pattern compared to prior studies.
• A substantial proportion (42.0%) of patients harbored rare or novel variants requiring further functional assessment.

Conclusions:

• NGS-based genetic testing is effective for diagnosing idiopathic DCM in the Korean population, identifying key causative genes.
• The presence of numerous unspecified variants highlights the need for comprehensive panels and advanced variant interpretation strategies.
• Integrating clinical and familial data is crucial for accurate genetic diagnosis and clinical decision-making in DCM.