Genetic testing for dilated cardiomyopathy in clinical practice

Area of Science:

• Cardiovascular Genetics
• Molecular Cardiology
• Genetic Diagnostics

Background:

• Dilated cardiomyopathy (DCM) frequently involves familial inheritance, with over 40 implicated genes.
• The clinical utility of genetic testing for DCM remains incompletely defined.
• This study investigated clinical genetic testing in a diverse DCM cohort to determine mutation prevalence and predictive factors.

Purpose of the Study:

• To characterize the prevalence and predictors of gene mutations in a diverse population of dilated cardiomyopathy (DCM) patients undergoing clinical genetic testing.
• To evaluate the utility of genetic testing in identifying causative mutations for DCM.
• To assess factors influencing the success rate of genetic testing in DCM.

Main Methods:

• Analyzed 264 unrelated adult and pediatric DCM index patients referred for clinical genetic testing.
• Performed genetic analysis on up to 10 key DCM-associated genes.
• Employed rigorous criteria to classify DNA variants as mutations, variants of unknown clinical significance (VUS), or benign.

Main Results:

• Mutations were identified in 17.4% of DCM patients, predominantly involving MYH7, LMNA, or TNNT2 genes.
• An additional 10.6% of patients had variants of unknown clinical significance (VUS).
• Genetic testing yielded positive results infrequently in older patients without a family history, while family history did not enhance sensitivity in pediatric cases.

Conclusions:

• Rigorous variant classification identified mutations in approximately 17% of diverse DCM index patients undergoing genetic testing.
• The current low sensitivity of genetic testing for DCM highlights limitations in methodology and gene discovery.
• Identification of mutations through genetic testing can significantly aid in guiding family management and clinical decision-making for DCM.