Heterozygous Arrhythmogenic Cardiomyopathy-desmoplakin Mutation Carriers Exhibit a Subclinical Cutaneous Phenotype with Cell Membrane Disruption and Lack of Intercellular Adhesion

Figures

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  Figure A1. Example of cardiac phenotype of included patients. (A): Pedigree of family according to the carrier status of the p.Arg2284* desmoplakin gene variant. Males and females are marked with squares and circles, respectively. Mutation carriers are marked with (E1-/+) and non-carriers with (E1-/-). Deceased individuals are annotated by a slash. Proband is indicated with black arrow. (B) and (C): classic ECG and CMR abnormalities for DSP gene carriers are illustrated (cases III-2 and III-7, respectively). The ECG (B) is characterized by low voltages and inverted/flattened T-waves. CMR demonstrates extensive circumferential subepicardial late gadolinium enhancement (C). (D): Non-sustained ventricular tachycardia (case III.2) during cardiopulmonary exercise testing.

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  Figure 1. Main findings in the immunohistochemistry study. (A): acantholytic areas evidenced in case 9 (Hematoxylin-Eosin ×200). (B): Acantholytic round cells. Some desmosomes (spines) are still observed between the round cells and adjacent keratinocytes (hematocillin-eosin ×400). (C): monilethrix. (D): negative expression of desmoplakin in case 4 (×200). (E): weak expression of desmoplakin in case 6 (×200).

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  Figure 2. The fingerprint sign. Keratinocytes with striated cytoplasm (Hematoxylin-Eosin ×1000).

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  Figure 3. Main findings in the electron microscope study. (A): keratinocytes of the spinous layer with abundant keratin filaments in cytoplasm. (B): keratinocytes with normal ultrastructural features (electron-dense midline, inner plaques and keratin filament junctions). (C): enlargement of the intercellular space between keratinocytes. (D): increase in the length of the cytoplasmic bridges. (E): Keratinocytes with unaffected structure.