Venous Thromboembolism in Myotonic Dystrophy Type 1

Investigators have identified in the cohort of 1084 patients presenting myotonic dystrophy type 1 (DM1) a 10% prevalence of venous thromboembolism (VTE) and a 7‰ annual incidence, which is 10-fold higher than in the general population and 3-fold compared to patients with other myopathies.

Patients' clinical presentations were very similar to those observed in patients with severe hypercoagulable states caused by mutations in genes encoding factors involved in coagulation, fibrinolysis or their regulation and represented a frequent cause of death.

To Investigator's knowledge, this association between VTE and DM1 has never been reported to date and no competing project has been initiated on this topic by any other team.

Investigators hypothesize that VTE in DM1 may be related to a hypercoagulable state resulting from an imbalance between coagulation processes and fibrinolysis properties. Because the expression of pathogenic CTG repeats in DM1 leads to a RNA gain-of-function mechanism, Investigators propose these abnormalities may be the consequence of alternative splicing misregulation and/or abnormal gene expression of coagulation, fibrinolysis factors or other factors involved in their regulation.

Investigators applied a candidate gene strategy to screen splicing profiles of 33 genes coding for haemostasis factors in a DM1 context. Using expression large-scale datasets of DM1 tissue samples from skeletal muscle and heart, Investigators identified splicing defects in 4 genes involved in haemostasis, in particular 3 involved in the fibrinolytic system: PLAT, PLAU and SERPINE1. These preliminary analyses were however not performed on liver samples whereas genes coding for haemostasis factors are synthesized and mainly expressed in liver. Analysis of liver and monocytes/megacaryotes RNA samples appears to be an essential step.