A novel heterozygous deletion-insertion mutation in the desmin gene causes complete atrioventricular block and mild myopathy

Abstract

Defects in the desmin gene have been identified in patients with cardiac and skeletal myopathy characterized by sarcoplasmic accumulation of desmin-positive deposits and electron dense granulofilamentous aggregates. We describe a desminopathy family with unusual clinical features of complete atrioventricular block and mild myopathy. The atrioventricular block can be found in each of the affected members sparing of the detectable cardiac structural abnormalities through echocardiogram. A novel heterozygous deletion-insertion mutation (c.1045-1063 del/G ins), deleting 7 amino acid (Met349-Arg355) and inserting 1 amino acid (Gly349) in a highly conserved alpha-helical 2B domain of desmin, has been identified. The results of this study indicate that atrioventricular conduction block without cardiac structural abnormalities may be an intrinsic feature of disease associated with specific desmin mutation. Furthermore atrioventricular conduction block may be an exclusive clinical manifestation and a major cause of disability and death in some patients with desmiopathy.