Résumé :
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Communication n° 619 Introduction: Laminopathies are a group of 10 heterogeneous disorders caused by mutations of LMNA gene encoding lamins A/C two nuclear envelope proteins. Among laminopathies three disorders specifically affect skeletal and cardiac muscles: Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy, type 1B (LGMD1B) and dilated cardiomyopathy with conduction system diseases (DCM-CD). Despite the growing number of reports in this field, no conclusive genotype-phenotype relations emerged. We developed the UMD-LMNA mutation database that collects genetic and clinical details of each individual carrying a LMNA mutation. Objectives: genotype-phenotype correlations in the laminopathies involving only striated muscles. Methods: Detailed clinical and genetic data of 363 LMNA mutated individuals were collected within the French EDMD and European EUROMEN networks. These data, gathered with those available in the literature (584 individuals), were collected into the UMD-LMNA database. Almost half of patients (511 out of 947) are affected by laminopathies involving only striated muscles. We selected patients with clinical data (271) and searched for genotype-phenotype correlations. Results: Mutations leading to the 3 striated laminopathies are evenly distributed along the LMNA gene. Analyses of mutation types showed that missense mutations and in-frame deletions/insertions lead to EDMD (74.7%), LGMD1B (17.6%) or DCM-CD (7.7%) while nonsense mutations and out-of-frame deletions/insertions are responsible for DCM-CD (50%), LGMD1B (30.6%) and EDMD (19.4%). Nevertheless no correlation was observed with skeletal or cardiac muscle involvement severities. Other parameters are currently under analysis. Conclusion: Despite clinical complexity of striated muscle laminopathies, "nonsense and truncating" mutational events lead preferentially to isolate cardiac disease while "missense and non truncating" events lead to cardiac and skeletal muscles involvement (EDMD/LGMD1B). These preliminary data should be confirmed on a larger group of patients.
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