Résumé :
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Communication n° 698 Background : Limb girdle muscular dystrophy type 2C (LGMD 2C) is a rare autosomal recessive muscular disorder caused by mutations in the gamma sarcoglycan (?-SG) gene. Patients with LGMD 2C frequently present with proximal and progressive muscular weakness before the age 10 and become wheelchair bound by age 12 in average. Cardiomyopathy and respiratory insufficiency may develop during the course of the disease and lead to a dismal prognosis and premature death. A phase I clinical gene therapy trial using an adeno-associated virus (AAV) vector harboring human ?-SG gene under the control of desmin promoter, is currently in preparation at Généthon and the Institute of Myology in Paris. The primary objective of this trial is to evaluate the safety of local intramuscular injection of the gene therapy product. Three dose levels will be evaluated and 9 patients will be considered in this study. Evaluations will last for 6 months for each patient. Preparing for this clinical trial, we have been reviewing clinical data from potential patients diagnosed at Cochin Hospital in Paris and La Timone Hospital in Marseille. Patients and methods : Patients from France and neighboring countries - including Mediterranean countries - with mutations in the ?-SG gene have been reviewed. Data included familial history, severity of the disease, associated heart disease and respiratory insufficiency, mutation and muscular biopsy data. Information was collected using the UMD-SGCG database developed by C. Béroud team in Montpellier. Results : 247 patients were reviewed. 200 were homozygous to del525T mutation, mostly patients from North African decent. 16 patients had associated cardiomyopathy and 18 had respiratory problems including tracheotomy. Biopsy data was available in 68 patients. Conclusion : LGMD 2C is a rare but yet a serious and disabling condition. Only a few series have been already published. Del525T is by far the most frequent mutation causing ?-sarcoglycanopathy. The clinical trial in preparation at Généthon and the Institute of Myology will address only patients bearing this mutation in the first step. Up-to-date clinical data concerning patients are needed to select more accurately candidates to the trial.
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