myotonic dystrophy - IDMC.org

Abstract No : 30
ORAL PRESENTATIONS
ANALYSIS OF CANDIDATE GENES MODIFIER FOR
THE CONDUCTION SYSTEM IMPAIRMENT IN MYOTONIC
DYSTROPHY TYPE 1 (DM1)
Vallo L., Bonifazi E., Rinaldi F., Contino G., Iraci R., Palladino A., Sannino P.,
Politano L., Botta A. and Novelli G.
Tor Vergata University-Via Montpellier 1,00133 Rome, Italy
Myotonic dystrophy type 1 (DM1) commonly includes cardiac involvement that typically occurs
because of myocardial fibrosis. The myocardial fibrosis typically manifests as conduction disturbances,
arrhythmias, ventricular dysfunction and sudden death. Atrio-ventricular block
(AVB) is one of the most frequent conduction alteration in DM1 and it is present in 20 % of
patients at baseline and 50 % at follow up. Mechanisms underlying the phenotypic heterogeneity
of heart involvement in the disease are still unclear. The aim of our study is to analyse
genes that could play a role in the phenotypic outcome of cardiac conduction abnormalities in
DM1 patients. We selected a set of candidate genes on a functional basis : LMNA (lamin A),
NK2.5 (NK2 transcription factor related, locus 5) and PRKAG2 (protein kinase, AMP-activated,
γ2). Our approach consists in an association study of intragenic polymorphic variants
with the AVB phenotype in genetically confirmed DM1 subjects. At this purpose, we recruited
32 DM1 patients showing AVB and 30 patients DM1-positive patients with no cardiac disease.
Genotyping has been performed using a combination of polymerase chain reaction-restriction
fragment length polymorphism (PCR-RFLP) and Taqman® real-time PCR technology. Statistical
analysis did not reveal any significant association of the selected genes with the AVB in DM1.
At present the characterization of other genes and the recruitment of a larger sample of affected
subjects are in progress.
QUEBEC 2005 51