Résumé :
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Context: Limb girdle muscular dystrophy (LGMD) type 2A is caused by mutation in the gene encoding for calpain-3 resulting into total or partial loss of protein. Diagnosis of LGMD2A, the most prevalent form of LGMD, is obtained by analyzing calpain-3 protein deficiency or CAPN3 gene mutation. Since there is no data from India regarding incidence of LGMD2A, this study was undertaken.Aims: To obtain frequency of LGMD2A in Indian population on the basis of protein analysis by immunoblotting and to correlate pathological and clinical features with protein analysis.Settings and Design: 203 muscle biopsies of clinically suspected LGMD, unclassified muscular dystrophy or myopathy were analyzed in a tertiary national referral centre for neurosciences.Methods and Material: Histopathological, immunohistochemical and enzyme histochemical analysis of muscle biopsies was performed followed by protein analysis for calpain-3 and dysferlin by immunoblotting. Results: During a period of 2 years (2009-2010), 730 muscle biopsies were received for various reasons and 203 were clinically diagnosed as LGMD. Of which 113 (55.6%) were diagnosed as calpainopathies, 52 (25.6%) as dysferlinopathies, 13 (6.4%) as sarcoglycanopathies and 25 (12.3%) remained unclassified. Immunoblot identified 113 patients with calpain-3 deficiency, of which 60 (53.1%) had complete loss and 53 (46.9%) had partial loss of calpain-3 protein. Associated dysferlin loss was seen in 30 (26.5%) patients. Calpainopathy comprised 55.6% all LGMDs. The biopsies of these patients displayed variety of morphological changes ranging from dystrophic pattern with presence of active fiber necrosis, regeneration and lobulated fibres (39; 34.5%) to end stage muscle disease. The mean age of presentation and disease onset was 23.9 and 17.4 years respectively. Calf hypertrophy was observed in 15 patients. Conclusions: These 113 cases constitute the confirmed cases of LGMD2A (calpainopathy) in India. It appears to be the most frequent form of LGMD in India, similar to the Western data. This study highlights the importance of immunoblotting for an accurate diagnosis of LGMD2A (calpainopathy). Key-words: LGMD2A, calpain-3, calpainopathy, immunoblotting, immunohistochemistry, lobulated fibres, India.
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