Mutations in the Lamin A/C gene mimic arrhythmogenic right ventricular cardiomyopathy

Eur Heart J. 2012 May;33(9):1128-36. doi: 10.1093/eurheartj/ehr451. Epub 2011 Dec 23.


Aims: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease predominantly caused by mutations in desmosomal protein genes. Lamin A/C gene (LMNA) mutations are associated with dilated cardiomyopathy, conduction abnormalities and high incidence of sudden cardiac death. In this study, we screened a large cohort of ARVC patients for LMNA mutations.

Methods and results: One hundred and eight patients from unrelated families with borderline (n = 27) or definite (n = 81) diagnosis of ARVC were genetically tested for five desmosomal genes and LMNA. Sixty-one (56.5%) were positive for desmosomal gene mutations. Standard polymerase chain reaction (PCR) amplification of the 12 protein-coding LMNA exons was performed and mutational screening performed by direct sequencing. Four patients (4%) without desmosomal gene mutations carried LMNA variants. Three had severe right ventricular involvement, and during follow-up three died (two suddenly and one from congestive heart failure); all three had conduction abnormalities on resting 12-lead electrocardiogram (ECG). Myocardial tissue from two patients showed myocyte loss and fibro-fatty replacement. In one of these, immunohistochemical staining with antibody to plakoglobin showed reduced/absent staining of the intercalated discs in the myocardium.

Conclusion: Lamin A/C gene mutations can be found in severe forms of ARVC. Lamin A/C gene should be added to desmosomal genes when genetically testing patients with suspected ARVC, particularly when they also have ECG evidence for conduction disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Arrhythmogenic Right Ventricular Dysplasia / diagnosis
  • Arrhythmogenic Right Ventricular Dysplasia / genetics*
  • Cytoskeletal Proteins / genetics
  • Desmosomes / genetics*
  • Diagnosis, Differential
  • Female
  • Humans
  • Lamin Type A / genetics*
  • Male
  • Middle Aged
  • Mutation, Missense / genetics*
  • Pedigree


  • Cytoskeletal Proteins
  • LMNA protein, human
  • Lamin Type A