Clinical cases of biventricular arrhythmogenic cardiomyopathy with a variant in the DES gene

Abstract

Mutations in the DES gene, which encodes the desmin protein, are associated with various forms of skeletal and/ or cardiac myopathies. Arrhythmogenic cardiomyopathy (ACM) due to a DES gene mutation is a rare form of desminopathy. In this article, we describe a familial case of biventricular ACM with early subclinical signs of myogenic involvement in the upper and lower limbs, initially manifesting with ventricular arrhythmias and progressive systolic dysfunction. Genetic analysis revealed a likely pathogenic variant c.358G>C (p.Ala120Pro, rs794728996) in exon 1 of the DES gene, located in the N-terminal region of the 1A helix domain. This variant affects filament assembly, leading to cytoplasmic aggregation of desmin, further supporting the functional importance of this region. Early implantation of an implantable cardioverter-defibrillator may contribute to primary prevention of sudden cardiac death in patients carrying this desmin variant. This is the first report of the phenotypic manifestations of the p.Ala120Pro variant in the DES gene in 2 patients with biventricular ACM from the same family.

Keywords

arrhythmogenic cardiomyopathy / desmin / systolic dysfunction / ventricular arrhythmia

References

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