Dilated cardiomyopathy with profound segmental wall motion abnormalities and ventricular arrhythmia caused by the R541C mutation in the LMNA gene

Saj, Michal; Jankowska, Agnieszka; Lewandowski, Michał; Szwed, Hanna; Szperl, Małgorzata; Płoski, Rafał; Bilińska, Zofia T.

doi:10.1016/j.ijcard.2008.12.083

Cited by 11 publications

(16 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These manifestations are very similar to those observed in patients harboring another substitution at the same position which replaces arginine with cysteine. 4,5,7 However, in addition to the exact location of the mutation, expression of this phenotype clearly depends on the specific amino acid change as evidenced by reports of p.R541S mutation 10 and p.R541H mutation, 15 both of which had no evidence of regional wall motion anomalies. It should be also mentioned that, in contrast to p.R541H mutation, in our patients there were no signs or symptoms of muscular dystrophy.…”

Section: Discussionmentioning

confidence: 99%

“…5 Assumption of possible LMNA mutation was based on similar phenotype reported in patients with p.R541C LMNA mutation initially described by Forrisier et al 4 (LV apical aneurysm, severe ventricular rhythm disturbances, left bundle branch block) and later by Hookana et al 7 (akinesis of the posterior LV wall, severe ventricular arrhythmias and sudden cardiac death) and by our group 5 (dyskinesis of the inferior LV wall, akinesis of the LV apex, severe ventricular arrhythmias and left bundle branch block). Analysis excluded presence of p.R541C but, interestingly revealed a previously undescribed mutation at the same position, with arginine to glycine substitution (c.1621 C4G, p.R541G) (Figure 3a).…”

Section: Case Reportmentioning

confidence: 99%

“…Interestingly, the molecular diagnosis was driven by phenotypic similarities with a previosuly described unrelated case of DCM harboring the p.R541C LMNA mutation. 5 …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A new c.1621 C>G, p.R541G lamin A/C mutation in a family with DCM and regional wall motion abnormalities (akinesis/dyskinesis): genotype–phenotype correlation

et al. 2010

Self Cite

View full text Add to dashboard Cite

Mutations in the lamin A/C gene (LMNA) are established causes of familial dilated cardiomyopathy (DCM) with atrio-ventricular block although relatively little is known about genotype-phenotype correlations. We describe a 23-year-old patient who presented with inferolateral wall thinning and akinesis with evidence of mid-myocardial fibrosis on cardiac magnetic resonance. Molecular analysis driven by clinical similarities with a previously described case harboring the p.R541C LMNA mutation revealed a novel c.1621 C4G, p.R541G substitution whose pathogenicity was confirmed by transfection of mouse myoblasts. Our results emphasize the role of LMNA mutations at position R541 in DCM cases with segmental LV wall motion akinesis/dyskinesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Case Reportmentioning

confidence: 99%

See 1 more Smart Citation

A new c.1621 C>G, p.R541G lamin A/C mutation in a family with DCM and regional wall motion abnormalities (akinesis/dyskinesis): genotype–phenotype correlation

et al. 2010

Self Cite

View full text Add to dashboard Cite

show abstract

“…Once a mutation was identified adult first-degree relatives of the mutation carriers were offered mutation screening. Individuals with a previously published [8,10,11] pathogenic LMNA mutations (p.Tyr481*, c.1443C > G; p.Arg541Cys, c.1621C > T; p.Arg541Gly, c.1621C > G) were included, when new follow-up data were available.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2013

View full text Add to dashboard Cite

BackgroundLMNA 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.MethodsBetween 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.ResultsWe 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.ConclusionsIn 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.

show abstract

“…Dilated forms of cardiomyopathy are characterized by ventricular chamber enlargement and systolic dysfunction with normal LV wall thickness [1].Among other causes [1][2][3][4][5][6][7][8], chronic excessive consumption of alcohol [1,9,10] has a very important presence. We present a case of a dilated alcoholic cardiomyopathy in a 65-year-old man.…”

Section: Case Reportmentioning

confidence: 99%

A dilated alcoholic cardiomyopathy

Lamari

Dattilo

Zito

et al. 2011

International Journal of Cardiology

View full text Add to dashboard Cite

Dilated cardiomyopathy with profound segmental wall motion abnormalities and ventricular arrhythmia caused by the R541C mutation in the LMNA gene

Cited by 11 publications

References 8 publications

A new c.1621 C>G, p.R541G lamin A/C mutation in a family with DCM and regional wall motion abnormalities (akinesis/dyskinesis): genotype–phenotype correlation

A new c.1621 C>G, p.R541G lamin A/C mutation in a family with DCM and regional wall motion abnormalities (akinesis/dyskinesis): genotype–phenotype correlation

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

A dilated alcoholic cardiomyopathy

Contact Info

Product

Resources

About