Genetic Overlap Between Dilated Cardiomyopathy and Neurological Disorders: Insights from a Next-Generation Sequencing
Maria Grazia Salluzzo1, Francesca A Schillaci1, Elisa Zago2
1Oasi Research Institute-IRCCS, 94018 Troina, Italy.
Diagnostics (Basel, Switzerland)
|August 13, 2026
Summary
Genetic variants in dilated cardiomyopathy (DCM) genes overlap with those linked to neurological disorders. This study identifies potential shared genetic pathways between these conditions, highlighting genes like TTN and FLNC.
Area of Science:
- Cardiovascular Genetics
- Neurogenetics
- Genomic Medicine
Background:
- Dilated cardiomyopathy (DCM) is a genetically diverse heart muscle disease.
- Growing evidence suggests shared genetic underpinnings between DCM and neurological disorders, indicating genetic pleiotropy.
- Understanding these overlaps can reveal common pathogenic pathways.
Purpose of the Study:
- To investigate the intersection of cardiac and neurological genetics in DCM patients.
- To identify candidate genes contributing to shared pathways between DCM and neurological conditions.
- To explore genetic pleiotropy between myocardial and neurological disorders.
Main Methods:
- Exome sequencing was performed on 149 DCM patients.
- In silico filtering was applied to a list of 211 inherited cardiomyopathy genes.
- Variants were classified using ACMG criteria, and gene associations with neurological disorders were reviewed via HGMD and literature searches.
Main Results:
- Genetic variants were found in 105 DCM patients, with TTN, FLNC, and MYH6 being the most frequently implicated genes.
- Several DCM-associated genes, including TTN, FLNC, RYR2, and SCN5A, showed reported links to neurological disorders like autism, Alzheimer's, and Parkinson's disease.
- A broad overlap in gene associations between cardiac and neurological phenotypes was observed.
Conclusions:
- Variants in TTN, FLNC, and MYH6 were most common in the studied DCM cohort.
- Multiple genes within the ClinGen DCM framework are independently associated with neurological disorders.
- Findings suggest gene-level co-annotation, but further research is needed to confirm shared mechanisms due to limitations like VUS prevalence and lack of neurological phenotyping.
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