Key result
LMNA mutations affect 8% of DCM patients and link to conduction disease and complex arrhythmias.
Why the study?
LMNA mutations are frequently involved in dilated cardiomyopathy with conduction disease, but their prevalence and clinical characteristics in Polish patients were not well defined.
Cross-Sectional (n=110)
No
LMNA mutations are present in approximately 8% of Polish patients with advanced or familial dilated cardiomyopathy and are strongly associated with conduction system disease and poor prognosis.
May support LMNA screening in DCM with conduction disease; extends European data but leaves open prospective validation.
BACKGROUND: LMNA mutations are most frequently involved in the pathogenesis of dilated cardiomyopathy with conduction disease. The goal of this study was to identify LMNA mutations, estimate their frequency among Polish dilated cardiomyopathy patients and characterize their effect both in vivo and in vitro. METHODS: Between January, 2008 and June, 2012 two patient populations were screened for the presence of LMNA mutations by direct sequencing: 66 dilated cardiomyopathy patients including 27 heart transplant recipients and 39 dilated cardiomyopathy patients with heart failure referred for heart transplantation evaluation, and 44 consecutive dilated cardiomyopathy patients, referred for a family evaluation and mutation screening. RESULTS: We detected nine non-synonymous mutations including three novel mutations: p.Ser431*, p.Val256Gly and p.Gly400Argfs*11 deletion. There were 25 carriers altogether in nine families. The carriers were mostly characterized by dilated cardiomyopathy and heart failure with conduction system disease and/or complex ventricular arrhythmia, although five were asymptomatic. Among the LMNA mutation carriers, six underwent heart transplantation, fourteen ICD implantation and eight had pacemaker. In addition, we obtained ultrastructural images of cardiomyocytes from the patient carrying p.Thr510Tyrfs*42. Furthermore, because the novel p.Val256Gly mutation was found in a sporadic case, we verified its pathogenicity by expressing the mutation in a cellular model. CONCLUSIONS: In conclusion, in the two referral centre populations, the screening revealed five mutations among 66 heart transplant recipients or patients referred for heart transplantation (7.6%) and four mutations among 44 consecutive dilated cardiomyopathy patients referred for familial evaluation (9.1%). Dilated cardiomyopathy patients with LMNA mutations have poor prognosis, however considerable clinical variability is present among family members.
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Saj et al. (2013) conducted a cross-sectional in Dilated cardiomyopathy (n=110). LMNA mutations vs. No LMNA mutations was evaluated on Prevalence of LMNA mutations. LMNA mutations were identified in 8% of Polish patients with dilated cardiomyopathy and were frequently associated with conduction disease and complex ventricular arrhythmias.
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