Clinical and mutational spectrum in a cohort of 105 unrelated patients with dilated cardiomyopathy

Genetics and Disease of Ventricular Muscle

“…More than 40 genes have been associated with a predominant clinical phenotype of adultonset DCM, and these encode diverse components of the sarcomere, Z-disc, cytoskeleton, sarcolemma, and nucleus (Table 1). Relatively few mutations have been identified in most of these genes, and the yield of genetic testing has been only 20% -30% (Hershberger and Siegfried 2011;Millat et al 2011;Teekakirikul et al 2013;van Spaendonck-Zwarts et al 2013). One notable exception is the LMNA gene, which causes DCM and conduction-system disease (Fatkin et al 1999(Fatkin et al , 2010.…”

Lamin A/C mutations in dilated cardiomyopathy

“…Ultimately, a better understanding of the pathogenesis of the disease may suggest novel strategies targeting the underlying molecular defects. [4,5,35] c.348_349insG p.Lys117GlufsX10 AVB, AF, SCD Coil 1B [36] c.356+1G>T n/a n/a Coil 1B [37] c.357-1G>T n/a LBBB, AF, PVB, VT, VF, HF Coil 1B [4,31,34] o -atrio-ventricular block degree, in parenthesis when degree specified only in some studies; AF -atrial fibrillation; AFL -atrial flutter; AN -axonal neuropathy; ASS -atrial standstill; ATC -atrial tachycardia; AVB -atrio-ventricular block; Br -bradycardia; CA -cardiac abnormalities; CCD -cardiac conduction disease; CMT2 -Charcot-Marie-Tooth disease; DCM -dilated cardiomyopathy; DM -diabetes mellitus; EDMD(2) -Emery-Dreifuss muscular dystrophy (type 2); FPLD -familial partial lipodystrophy; HF -heart failure; IVB -intra-ventricular block; ICD -implantable cardiac defibrillator; LAFB -left anterior fascicular block; LBBB -left bundle branch block;…”

“…However, wild type lamin A transfected alone has consistently shown to localize to the inner nuclear lamina with some nucleoplasmic localization. Conversely, lamin C has been shown to localize as intranuclear aggregate [18,[32][33][34][35][36]. Intranuclear lamin C has shown to be more mobile than intranuclear lamin A [36,37].…”

Doubly heterozygous LMNA and TTN mutations revealed by exome sequencing in a severe form of dilated cardiomyopathy

“…[6][7][8] Similarly, compound and digenic heterozygosity were identified in patients with arrhythmogenic right ventricular cardiomyopathy, whereby several desmosome and celljunction genes were found to carry more than one mutation likely associated with low penetrance. 9 It is to be expected that similar modifiers exist for DCM; even though a single case of a 14-year-old boy with manifestations of DCM and mutations in both MYH7 and TNNT2 has been published, 10 little is known about the genes and the molecular mechanisms involved in modifying the phenotype of familial DCM.…”