Key result
SCN5A c.611C>A variant linked to early-onset DCM and Purkinje-related premature contractions, particularly with PRKAG2 mutations.
Why the study?
To describe a 3-generation family with a rare SCN5A c.611C>A variant presenting with DCM and MEPPC, and investigate why carriers of the same variant exhibited different phenotypes.
Case Report (n=15)
No
The SCN5A c.611C>A variant is associated with DCM and MEPPC, and co-inheritance with a PRKAG2 mutation can cause a severe, early-onset cardiomyopathy phenotype.
Should not yet change genetic testing or management in DCM; hypothesis-generating for SCN5A-PRKAG2 digenic effects.
Objective We report a 3-generation family with SCN5A c.611 C>A rare variant, whose clinical characteristics are dilated cardiomyopathy (DCM) combined with multifocal ectopic Purkinje-related premature contractions (MEPPC). We tried to explain why the same SCN5A variant carriers had different phenotypes. Methods We collected the clinical data from the family, and followed up this family members. Genetic testing was done for whom DNA samples could be collected. Results Information was collected from 15 people in this family, 8 of whom had genetic testing. The SCN5A variant was present in all patients of this family, whose clinical features showed DCM combined with MEPPC. The proband's children developed DCM and MEPPC in their childhood. They both carried a SCN5A p.A204E mutation from their mother and a mutation PRKAG2 p.D372N from their father. The son did heart transplant and his heart was both dilated and thickened. The pathology confirmed the presence of glycogen accumulation in the myocardium, which were consistent with the diagnosis of PAKAG2 syndrome. Conclusion SCN5A c.611 C>A variant was related to DCM combined with MEPPC. This case report is the first to demonstrate that a combination of SCN5A and PRKAG2 mutations can cause DCM plus MEPPC and PRKAG2 Syndrome.
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Huang et al. (2022) conducted a case report in Dilated cardiomyopathy and arrhythmia (n=15). Genetic testing (SCN5A and PRKAG2 mutations) was evaluated on Presence of dilated cardiomyopathy and multifocal ectopic Purkinje-related premature contractions. The SCN5A c.611C>A variant, particularly when combined with a PRKAG2 mutation, was associated with early-onset dilated cardiomyopathy and multifocal ectopic Purkinje-related premature contractions.
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