LMNA mutations in Polish patients with dilated cardiomyopathy: prevalence, clinical characteristics, and in vitro studies

dc.contributor.authorSaj, Michal
dc.contributor.authorBilinska, Zofia T
dc.contributor.authorTarnowska, Agnieszka
dc.contributor.authorSioma, Agnieszka
dc.contributor.authorBolongo, Pierrette
dc.contributor.authorSobieszczanska-Malek, Malgorzata
dc.contributor.authorMichalak, Ewa
dc.contributor.authorGolen, Dorota
dc.contributor.authorMazurkiewicz, Lukasz
dc.contributor.authorMalek, Lukasz
dc.contributor.authorWalczak, Ewa
dc.contributor.authorFidzianska, Anna
dc.contributor.authorGrzybowski, Jacek
dc.contributor.authorPrzybylski, Andrzej
dc.contributor.authorZielinski, Tomasz
dc.contributor.authorKorewicki, Jerzy
dc.contributor.authorTesson, Frederique
dc.contributor.authorPloski, Rafal
dc.identifier.citationBMC Medical Genetics. 2013 May 23;14(1):55
dc.description.abstractAbstract 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.
dc.titleLMNA mutations in Polish patients with dilated cardiomyopathy: prevalence, clinical characteristics, and in vitro studies
dc.typeJournal Article
dc.rights.holderSaj et al.; licensee BioMed Central Ltd.
CollectionLibre accès - Publications // Open Access - Publications