© 2005 European Society of Cardiology
Genetic and phenotypic analysis of dilated cardiomyopathy with conduction system disease: Demand for strategies in the management of presymptomatic lamin A/C mutant carriers
a Charité- Universitätsmedizin Berlin/Kardiologie am Campus Buch and Virchow-Klinikum, und Max-Delbrück-Centrum für Molekulare Medizin Wiltbergstr. 50, 13125 Berlin, Germany
b Universitätsklinikum der Friedrich-Schiller-Universität Jena Klinik für Innere Medizin I, Kardiologie, Erlanger Allee 101, 07740 Jena, Germany
c Krankenhaus Reinbeck Hamburger Str. 41, 21465 Hamburg, Germany
d Charité- Universitätsmedizin Berlin/Gastroenterologie Hepatologie & Endokrinologie, Campus Mitte, Schumannstr. 20/21, 10117 Berlin, Germany
e Deutsches Herzzentrum Berlin/Herz-und Gefässchirurgie Augustenburger Platz 1, 13353 Berlin, Germany
* Corresponding author. Tel.: +49 30 9417 2508; fax: +49 30 9417 2279. E-mail address: perrot{at}fvk-berlin.de (A. Perrot)
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Abstract |
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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.
Key Words: Lamin A/C • LMNA • Mutation • Familial dilated cardiomyopathy • DCM • Conduction system disease
Received February 14, 2005; Revised July 29, 2005; Accepted November 8, 2005
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