FIGURE 1

Clinical presentation. (A) Upper panel: transverse section of the ACM patient's explanted heart. The right ventricle (RV) is dilated. Adipo–fibrotic replacement of the myocardium is also observed. Lower panel: Microscopic section of the patient's explanted heart stained with hematoxylin, eosin and safran. Inflammation, adipose tissue and myocardial necrosis are observed. IT, interstitial tissue; INF, inflammation; FI, adipose tissue; MN, myocardial necrosis. (B) Twelve‐lead surface ECG illustrating the patient's electrical profile. The patient was in sinus rhythm with a PR interval at 160 ms, QRS interval at 120 ms and S wave slurring. Negative T waves were observed in V2 through V5. (C) Family pedigree. The index patient (II.1) is indicated by a red arrow. Individuals indicated with a red cross carry the mutation (II‐1 and III‐1). (D) Electropherogram of the patient's DNA showing the DSC2 mutation responsible for the R132C substitution. (E) Multispecies protein sequence alignment illustrating the high degree of conservation of the arginine at position 132 (highlighted in grey). (F) Two‐dimensional schematic of the DSC2 protein sequence showing the propeptide and cleavage site. Arginine 132 is located at the junction of the propeptide and the mature protein. (G) DSC2 protein sequence illustrating the location of arginine 132 within the cleavage site. Cleavage activates desmocollin's adhesive properties