Apical left ventricular aneurysm without atrio‐ventricular block due to a lamin A/C gene mutation

Abstract

Background: Mutations in LMNA gene encoding two ubiquitously expressed nuclear proteins, lamins A and C, give rise to up to 7 different pathologies affecting specific tissues. Three of these disorders affect cardiac andyor skeletal muscles with atrioventricular conduction disturbances, dilated cardiomyopathy and sudden cardiac death as common features. Results: A new LMNA mutation (1621C)T, R541C) was found in two members of a French family with a history of ventricular rhythm disturbances and an uncommon form of systolic left ventricle dysfunction. The two patients: the proband and his daughter, were affected and exhibited an atypical form of dilated cardiomyopathy with an unexplained left ventricle aneurysm revealed by ventricular rhythm disturbances without atrio-ventricular block. Conclusion: This finding reinforces the highly variable phenotypic expression of LMNA mutation and emphasizes the fact that LMNA mutations can be associated with different cardiac phenotypes.

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

“…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.…”

“…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).…”

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

“…described the presence of this mutation manifesting as an apical LV aneurysm and ventricular tachyarrhythmias [2].…”

Novel c.367_369del LMNA mutation manifesting as severe arrhythmias, dilated cardiomyopathy, and myopathy

“…17 Cardiac involvement may precede the skeletal muscle affection. 15 Dilated cardiomyopathy and cardiac conduction abnormalities with a strong tendency toward sudden cardiac death were reported in missense mutations, 2,5,12,18,19 nonsense mutations, 20 splice site mutations, 3,14,19,21,22 duplication/in-frame insertions, 19 and deletions. [2][3][4]11,13,19,[23][24][25][26] Mutations in LMNA resulting in cardiac abnormalities are most frequently located in exon 3, 5,13,25-27 exon 1, [28][29][30] or in the splice-receptor sequence of intron 6.…”