Genetic and phenotypic analysis of dilated cardiomyopathy with conduction system disease: Demand for strategies in the management of presymptomatic lamin A/C mutant carriers

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Item Type:	Article
Title:	Genetic and phenotypic analysis of dilated cardiomyopathy with conduction system disease: Demand for strategies in the management of presymptomatic lamin A/C mutant carriers
Creators Name:	Perrot, A., Sigusch, H.H., Naegele, H., Genschel, J., Lehmkuhl, H., Hetzer, R., Geier, C., Perez, L.V., Reinhard, D., Dietz, R., Osterziel, K.J. and Schmidt, H.H.
Abstract:	BACKGROUND: One-third of cases of dilated cardiomyopathy (DCM) is of familial aetiology. Several genes have been reported to cause the autosomal dominant form of DCM. AIMS: To analyze the lamin A/C gene (LMNA) in 31 unrelated patients with DCM and conduction system disease (CSD). METHODS: Patients and family members underwent physical examination, ECG/Holter-ECG, echocardiography, and selective coronary angiography. Genetic analysis of all coding exons of LMNA was performed using PCR and sequencing. RESULTS: Three different LMNA mutations (Arg377His, c.1397delA, c.424_425ins21nt) were identified in three families with autosomal dominant disease comprised of 39 individuals. 21 individuals were mutation carriers, of whom 12 were symptomatic. We observed a progressive and age-dependent form of DCM with CSD and arrhythmias. First, the patients developed a moderate left ventricular dilatation without symptoms. Later, systolic function declined progressively and the patients became symptomatic resulting in a high mortality due to sudden death and heart failure. CONCLUSIONS: Genetic screening leads to the identification of symptomatic and asymptomatic mutant carriers. The latter at a young age should be regarded as 'presymptomatic' because of the age-dependent disease manifestation. New guidelines are required for the management of these individuals.
Keywords:	Lamin A/C, LMNA, Mutation, Familial Dilated Cardiomyopathy, DCM, Conduction System Disease
Source:	European Journal of Heart Failure
ISSN:	1388-9842
Publisher:	Elsevier
Volume:	8
Number:	5
Page Range:	484-493
Date:	August 2006
Additional Information:	The original publication is available at www.sciencedirect.com
Official Publication:	https://doi.org/10.1016/j.ejheart.2005.11.004
PubMed:	View item in PubMed

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