Desmosomal Protein Gene Mutations in Patients With Idiopathic Dilated Cardiomyopathy Undergoing Cardiac Transplantation: A Clinopathological Study

Study Questions:

What is the frequency of desmosomal protein gene mutations in receipts of heart transplants compared with the general population, and does their histopathology differ?


This was a single-center, nonblinded study of 89 unrelated patients requiring cardiac transplant for end-stage dilated cardiomyopathy in Madrid, Spain. Five arrhythmogenic right ventricular (RV) dysplasia desmosome coding genes were tested by serum polymerase chain reaction, and the frequency of having a defect was compared with 200 controls without cardiomyopathy. Cardiac architecture was examined from explanted hearts.


The mean ± standard deviation patient age was 49 ± 13 years, 100% were Caucasian, and 80% were male. On genetic screening, 13% (n = 12) of patients had pathogenic desmosome mutations and 6% (n = 5) had genetic variants of unknown pathogenicity. No control patient had desmosome gene abnormalities. Forty-two percent of patients with desmosome defects had a family pedigree consistent with familial heart failure compared with 15% of patients without gene abnormalities (p = 0.08). On histopathologic evaluation, 39% (n = 35) and 81% (n = 72) of explanted hearts had fatty infiltration in the right and/or left ventricle, respectively, and 50% (n = 45) and 80% (n = 71) had fibrosis, respectively. The prevalence of fibrosis and/or fatty infiltration did not differ amongst mutation carriers and noncarriers. The pretransplant burden of atrial or ventricular arrhythmias, time on transplant wait list, and RV ejection fraction did not differ based on gene status.


Desmosomal gene mutations are frequent in patients with dilated cardiomyopathy requiring transplant, but these mutations do not confer differences in pretransplant clinical characteristics or histopathology.


Desmosomal gene mutations have classically been associated with the development of RV dysplasia, a disease associated with fibrofatty infiltration of the right and left ventricles, ventricular arrhythmias, and heart failure development. In this study, the authors demonstrated desmosomal defects in over 13% of patients with dilated cardiomyopathy requiring transplant. However, these patients did not demonstrate classic RV dysplasia findings on histopathological analysis. While there was a trend toward more atrial fibrillation in the desmosome gene mutation group, ventricular dysrhythmias were not more frequent. In contrast, gene carriers appeared more likely to describe a family history of heart failure on pedigree analysis. This suggests that desmosome gene mutations confer different phenotypes in different patients, and do not carry a high penetrance. Overall, this further complicates the utility of genetic testing in cardiomyopathy diagnosis and inheritance.

Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Genetic Arrhythmic Conditions, SCD/Ventricular Arrhythmias, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Acute Heart Failure, Heart Transplant, Interventions and Structural Heart Disease

Keywords: Heart Atria, Genetic Testing, Cost of Illness, Heart Transplantation, Heart Diseases, Mutation, Arrhythmogenic Right Ventricular Dysplasia, Pedigree, Virulence, Heart Failure, Spain, Cardiomyopathy, Dilated

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