title: Mutations in the Lamin A/C gene mimic arrhythmogenic right ventricular cardiomyopathy.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Heart Hospital, University College London Hospitals Trust, 16-18 Westmoreland Street, London W1G 8PH,  UK.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Quarta
authors.forename: Petros
authors.initials: P
authors.lastname: Syrris
authors.forename: Michael
authors.initials: M
authors.lastname: Ashworth
authors.forename: Sharon
authors.initials: S
authors.lastname: Jenkins
authors.forename: Krisztina
authors.initials: K
authors.lastname: Zuborne Alapi
authors.forename: John
authors.initials: J
authors.lastname: Morgan
authors.forename: Alison
authors.initials: A
authors.lastname: Muir
authors.forename: Antonios
authors.initials: A
authors.lastname: Pantazis
authors.forename: William J
authors.initials: WJ
authors.lastname: McKenna
authors.forename: Perry M
authors.initials: PM
authors.lastname: Elliott
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000175:diagnosis / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics; D003896:Desmosomes / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree
chemical_list: D003598:Cytoskeletal Proteins; C494847:LMNA protein, human; D034904:Lamin Type A