The ACTN2 variant p.Tyr473Cys is associated with a dominantly inherited phenotype suggestive of left-dominant arrhythmogenic cardiomyopathy and reduced plakoglobin signal on myocardial biopsy.
Case Report
The ACTN2 gene should be considered in genetic screening for patients with arrhythmogenic cardiomyopathy, as the p.Tyr473Cys variant is associated with a left-dominant phenotype and plakoglobin deficiency.
Key Teaching Points•The variant p.Tyr473Cys in the ACTN2 gene, coding for the Z-disk protein alpha-actinin-2, leads to a dominantly inherited phenotype suggestive of left-dominant arrhythmogenic cardiomyopathy (ACM). This implies that analysis of ACTN2 might be considered in patients with ACM in whom genetic screening was inconclusive.•The signal for plakoglobin was markedly reduced in the myocardial biopsy of our index case. This further supports the concept that plakoglobin deficiency may be a common feature of ACMs, independently of their molecular origin.•The decreased signal for plakoglobin in the myocardial biopsy of our index case suggests a link between Z-disc proteins and the desmosome. This remains to be investigated. •The variant p.Tyr473Cys in the ACTN2 gene, coding for the Z-disk protein alpha-actinin-2, leads to a dominantly inherited phenotype suggestive of left-dominant arrhythmogenic cardiomyopathy (ACM). This implies that analysis of ACTN2 might be considered in patients with ACM in whom genetic screening was inconclusive.•The signal for plakoglobin was markedly reduced in the myocardial biopsy of our index case. This further supports the concept that plakoglobin deficiency may be a common feature of ACMs, independently of their molecular origin.•The decreased signal for plakoglobin in the myocardial biopsy of our index case suggests a link between Z-disc proteins and the desmosome. This remains to be investigated.
Good et al. (Mon,) conducted a case report in Left-dominant arrhythmogenic cardiomyopathy. ACTN2 variant p.Tyr473Cys was evaluated. The ACTN2 variant p.Tyr473Cys is associated with a dominantly inherited phenotype suggestive of left-dominant arrhythmogenic cardiomyopathy and reduced plakoglobin signal on myocardial biopsy.