Desmin c.322G>A variant is associated with cardiomyopathy: a case series

Desmin is a critical intermediate filament protein in muscle cells that maintains myofibril integrity and proper force transmission. Rare variants in the DES gene are known to cause cardiomyopathy with or without concomitant skeletal myopathy.

We identified the c.322G>A p.(Glu108Lys) variant in the DES gene (NM_001927.4) in three unrelated patients, all of whom exhibited arrhythmic manifestations and progressive left ventricular (LV) dysfunction over time. Additionally, two other patients harboring the same variant presented with a nondilated left ventricular cardiomyopathy (NDLVC) phenotype defined by the presence of nonischemic LV scarring or global LV hypokinesia in the absence of LV dilatation.

The classification of the DES c.322G>A p.(Glu108Lys) variant has been debated. However, the clinical features observed in the reported cases strengthen the evidence supporting its likely pathogenic role in cardiomyopathy.