Multiple mutations in desmosomal proteins encoding genes in arrhythmogenic right ventricular cardiomyopathy/dysplasia

A: Sequence electropherograms showing the detected mutations. Numbering of the nucleotides starts at the ATG codon. B: Evolutionary conservation of the missense mutations identified in desmoplakin, desmoglein-2, and plakophilin-2 genes, among different species. The mutated amino acids are in red.

Pedigrees of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) probands carrying multiple mutations. Arrows indicate index cases. + and – denote the presence or absence of a desmosomal gene mutation.

Clinical findings of index case (IV,5) of family #137. A: Twelve-lead electrocardiogram with presence of intraventricular conduction delay, negative T waves in precordial and inferior leads, and low QRS voltages. B: Two-dimensional echocardiogram showing a severe RV dilatation with moderate systolic depression. The LV is also dilated. C: Histological section of the RV free wall at high magnification; residual hypertrophied myocytes are entrapped within fibrous and fatty tissue (Heidenhain trichrome). D: Severe myocyte abnormalities with bizarre dysmorphic and dysmetric nuclei and perinuclear halo (hematoxylin-eosin). LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle.