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Expanding the phenotype of LMNA mutations in dilated cardiomyopathy and functional consequences of these mutations
  1. P Sébillon1,2,
  2. C Bouchier1,2,
  3. L D Bidot1,2,
  4. G Bonne2,3,
  5. K Ahamed1,2,
  6. P Charron1,2,4,
  7. V Drouin-Garraud5,
  8. A Millaire6,
  9. G Desrumeaux7,
  10. A Benaïche1,2,
  11. J-C Charniot8,
  12. K Schwartz2,3,
  13. E Villard1,2,
  14. M Komajda1,2,4
  1. 1Laboratoire Génétique et Insuffisance Cardiaque, Association Claude Bernard/Université Paris VI, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
  2. 2IFR 14 Cœur, Muscles et Vaisseaux, Paris, France
  3. 3U582 INSERM, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
  4. 4Service de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
  5. 5Service de Génétique, CHU Rouen, France
  6. 6Service de Cardiologie C, Centre Hospitalier Régional Universitaire, Lille, France
  7. 7Institut de Cardiologie, CHU Rouen, France
  8. 8Service de Cardiologie, Hôpital Avicenne, Bobigny, France
  1. Correspondence to:
 Dr P Sébillon, Laboratoire Génétique et Insuffisance Cardiaque, Pavillon Rambuteau, Groupe Hospitalier Pitié-Salpêtrière, 47 bd de l’Hôpital, 75651 Paris Cedex 13, France; 


Aims: Mutations in the lamin A/C gene (LMNA) have been reported to be involved in dilated cardiomyopathy (DCM) associated with conduction system disease and/or skeletal myopathy. The aim of this study was to perform a mutational analysis of LMNA in a large white population of patients affected by dilated cardiomyopathy with or without associated symptoms.

Methods: We performed screening of the coding sequence of LMNA on DNA samples from 66 index cases, and carried out cell transfection experiments to examine the functional consequences of the mutations identified.

Results: A new missense (E161K) mutation was identified in a family with early atrial fibrillation and a previously described (R377H) mutation in another family with a quadriceps myopathy associated with DCM. A new mutation (28insA) leading to a premature stop codon was identified in a family affected by DCM with conduction defects. No mutation in LMNA was found in cases with isolated dilated cardiomyopathy. Functional analyses have identified potential physiopathological mechanisms involving identified mutations, such as haploinsufficiency (28insA) or intermediate filament disorganisation (E161K, R377H).

Conclusion: For the first time, a specific phenotype characterised by early atrial fibrillation is associated with LMNA mutation. Conversely, mutations in LMNA appear as a rare cause of isolated dilated cardiomyopathy. The variable phenotypes observed in LMNA-DCM might be explained by the variability of functional consequences of LMNA mutations.

  • cardiomyopathy
  • atrial fibrillation
  • molecular genetics
  • lamin A/C

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