Résumé :
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OBJECTIVE: To determine the distribution of subtypes of Limb-Girdle Muscular Dystrophy (LGMD) among patients in South-East of France. To determine the proportion of patients in whom a molecular diagnosis was available. BACKGROUND: LGMD are a heterogeneous group of genetically determined disorders with a primary or predominant involvement of the pelvic or shoulder girdle musculature. Twenty loci have been so far identified, seven autosomal dominant and thirteen autosomal recessive. DESIGN / METHODS: We retrospectively analyzed clinical and histopathological data from 154 patients with a progressive LGMD phenotype. Dystrophinopathy, congenital muscular dystrophy, myotonic dystrophy, facio-scapulo-humeral muscular dystrophy, inflammatory, congenital, metabolic myopathies or patients with insufficient data were excluded. We selected 56 patients. Muscle biopsy provided histopathology and immunodiagnostic testing. The protein abnormality along with clinical features directed mutation screening. RESULTS : From this evaluation, the distribution of the immunophenotypes was : 12.5% dysferlin deficiency followed by 10.7 % sarcoglycans, 10.7% calpain-3, 8.9% dystroglycans, 1.7% caveolin-3 and 1.7% myotilin deficiencies. In 42.8 % of all patients, a classifying diagnosis was made. The relative frequency of the subtypes was : 17.8% dysferlinopathy, 12.5% FKRP, 7.1% alpha-sarcoglycanopathy, 5.3% calpainopathy, 1.8% caveolinopathy and 57.2% undetermined. Several new mutations in LGMD2A and 2B patients have been found in this population. CONCLUSIONS / RELEVANCE Dysferlinopathy was the most frequent subtype of this population followed by LGMD2I. The proportion of classifying diagnosis is similar to previous studies. Further genetic analysis of this LGMD population is needed. In dystroglycans phenotypes with no FKRP mutations, mutation analysis in various genes, namely LARGE, POMT1, POMT2, fukutin, and POMGnT1 could be performed.
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