title: Cardiac arrest and left ventricular fibrosis in a Finnish family with the lamin A/C mutation.
abstract: BACKGROUND
  We screened the candidate genes from a Finnish family in which the mother was resuscitated from ventricular fibrillation and the daughter died suddenly without any prior cardiac symptoms.
  
  
  RESULTS
  In addition to screening of potential structural gene mutations, phenotyping of the proband and medico-legal autopsy of the victim of the sudden death, including histopathological examinations, were performed. Genetic screening revealed an R541C mutation in the lamin A/C gene both in the proband and her daughter. None of the 16 first- or second-degree relatives, or 96 unrelated healthy subjects, carried the same mutation. In the proband, the size and the global function of the left ventricle (LV) were normal, but a local hypokinesia and thinning of inferoposterior area of the LV were seen in 2D echocardiography and magnetic resonance imaging. Coronary angiogram and the results of the electrophysiological study were normal. Autopsy of the victim of sudden death showed localized thinning and fibrosis in the inferoposterior area of the LV, with only minimal fibrosis in the right ventricle and no abnormalities in the interventricular septum.
  
  
  CONCLUSIONS
  These observations indicate that a fatal or near-fatal cardiac arrhythmia can be the first clinical manifestation of a "de novo" mutation R541C of the lamin A/C gene. Replacement of cardiac myocytes by fibrosis seems to be the predominant pathologic-anatomic finding.
authors.affiliation: Division of Cardiology, Department of Medicine, University of Oulu, Oulu, Finland.
authors.forename: Eeva
authors.initials: E
authors.lastname: Hookana
authors.forename: M Juhani
authors.initials: MJ
authors.lastname: Junttila
authors.forename: Terttu
authors.initials: T
authors.lastname: Särkioja
authors.forename: Raija
authors.initials: R
authors.lastname: Sormunen
authors.forename: Matti
authors.initials: M
authors.lastname: Niemelä
authors.forename: M J Pekka
authors.initials: MJ
authors.lastname: Raatikainen
authors.forename: Paavo
authors.initials: P
authors.lastname: Uusimaa
authors.forename: Eric
authors.initials: E
authors.lastname: Lizotte
authors.forename: Keijo
authors.initials: K
authors.lastname: Peuhkurinen
authors.forename: Ramon
authors.initials: R
authors.lastname: Brugada
authors.forename: Heikki V
authors.initials: HV
authors.lastname: Huikuri
mesh_terms: D000293:Adolescent; D000328:Adult; D004719:Endomyocardial Fibrosis / Q000175:diagnosis* / Q000235:genetics*; D005190:Family; D005260:Female; D005387:Finland; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008070:Lipopolysaccharides; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis* / Q000235:genetics*
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A; D008070:Lipopolysaccharides; C050016:lipoarabinomannan