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Desmosomal protein gene mutations in patients with idiopathic dilated cardiomyopathy undergoing cardiac transplantation: a clinicopathological study
  1. Pablo Garcia-Pavia1,
  2. Petros Syrris2,
  3. Clara Salas3,
  4. Alison Evans2,
  5. Jesus G Mirelis1,
  6. Marta Cobo-Marcos1,
  7. Carlos Vilches4,
  8. Belen Bornstein5,
  9. Javier Segovia1,
  10. Luis Alonso-Pulpon1,
  11. Perry M Elliott2
  1. 1Cardiomyopathy Unit, Heart Failure and Heart Transplant Section, Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain
  2. 2Inherited Cardiovascular Disease Unit, The Heart Hospital, University College London, London, UK
  3. 3Department of Pathology, Hospital Universitario Puerta de Hierro, Madrid, Spain
  4. 4Department of Immunology, Hospital Universitario Puerta de Hierro, Madrid, Spain
  5. 5Department of Biochemistry, Hospital Universitario Puerta de Hierro, Madrid, Spain
  1. Correspondence to Dr Pablo Garcia-Pavia, Cardiomyopathy Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, Manuel de Falla 2, 28222 Madrid, Spain; pablogpavia{at}


Backgroud Idiopathic dilated cardiomyopathy (DCM) is the most frequent indication for orthotopic heart transplantation. It has been suggested that mutations in genes encoding desmosomal proteins, more typically associated with arrhythmogenic right ventricular cardiomyopathy, are a cause of DCM.

Objectives To determine the frequency of desmosomal protein gene mutations in heart transplant recipients and their families and to examine histopathological characteristics of explanted organs from mutation carriers.

Methods 89 unrelated patients aged 47.9±13.5 years (80% male) transplanted for end-stage DCM underwent genetic screening of five desmosomal genes (PKP2, DSP, DSC2, DSG2 and JUP). The findings were correlated with clinical features and histological characteristics in explanted hearts.

Results Pathogenic mutations were identified in 12 patients (13%). Five additional patients (6%) had genetic variants of unknown significance. The clinical phenotype of patients with pathogenic mutations was indistinguishable from that observed in patients without mutations. Evaluation of 76 relatives from 14 families with sequence variants (11 with pathogenic mutations and three with variants of unknown effect) identified 38 mutation carriers, four of whom had an overt DCM phenotype. Evidence of co-segregation of mutations with DCM phenotype was found in five families. Histological evaluation of explanted hearts did not show any specific features in patients with pathogenic mutations.

Conclusions Mutations in desmosomal genes are frequent in patients with advanced DCM undergoing cardiac transplantation. These findings emphasise the importance of familial evaluation and genetic counselling in patients with end-stage DCM and pose important challenges for current histopathological criteria for arrhythmogenic right ventricular cardiomyopathy.

  • Idiopathic dilated cardiomyopathy
  • arrhythmogenic right ventricular cardiomyopathy
  • desmosomal proteins
  • cardiac transplant
  • heart transplant
  • genetics
  • cardiomyopathy dilated

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  • Funding This work was partially supported by the Instituto de Salud Carlos III (grant PI08/0978) and the Spanish Ministry of Health (Red Cooperativa de Insuficiencia Cardiaca (REDINSCOR) (RD06/03/0018). Some of this work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Hospital Universitario Puerta de Hierro and complies with the principles of the declaration of Helsinki.

  • Provenance and peer review Not commissioned; externally peer reviewed.