This study was supported by grants from the Sigfrid Juselius Foundation, Helsinki, Finland, and the Finnish Foundation for Cardiovascular Research, Helsinki, Finland.
Cardiac Arrest and Left Ventricular Fibrosis in a Finnish Family with the Lamin A/C Mutation
Version of Record online: 21 NOV 2007
© 2008 Wiley Periodicals, Inc.
Journal of Cardiovascular Electrophysiology
Volume 19, Issue 7, pages 743–747, July 2008
How to Cite
HOOKANA, E., JUNTTILA, M. J., SÄRKIOJA, T., SORMUNEN, R., NIEMELÄ, M., RAATIKAINEN, M.J. P., UUSIMAA, P., LIZOTTE, E., PEUHKURINEN, K., BRUGADA, R. and HUIKURI, H. V. (2008), Cardiac Arrest and Left Ventricular Fibrosis in a Finnish Family with the Lamin A/C Mutation. Journal of Cardiovascular Electrophysiology, 19: 743–747. doi: 10.1111/j.1540-8167.2007.01017.x
Manuscript received 20 June 2007; Revised manuscript received 19 September 2007; Accepted for publication 20 September 2007.
- Issue online: 25 JUL 2008
- Version of Record online: 21 NOV 2007
- lamin A/C gene mutation;
- ventricular fibrillation;
- sudden cardiac death;
- left ventricle fibrosis;
- medico-legal autopsy
Introduction: 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.
Methods and 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.
Conclusion: 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.