Clinical and pathological features of the 5 Limb-girdle muscular dystrophy 2A patients

Abstract

Objective To investigate the clinical and molecular pathological features of limb-girdle muscular dystrophy 2A (LGMD2A) of Chinese patients. Methods Thirty cases of LGMD with excluding LGMD2B were included in this study. The muscle specimens were performed by a standard series methods of histochemistry, enzymohistochemistry, immunohistochemistry and Western blot. The clinical and molecular pathological features of LGMD2A were retrospective analyzed. Results Five cases with no or only trace expression of calpain-3 protein were diagnosed as calpainopathy (LGMD2A) by Western blot analysis. The age of onset of these 5 patients ranged from 10 to 45 years and the duration of the disease were about 2-10 years. Proximal muscles weakness and atrophy of lower limbs were predominantly involved. In all patients,symptoms progressed slowly. The ambulation could be retained for many years but running and jumping were impaired early. The serum creatine kinase level was elevated moderately to markedly. Electromyography showed myopathic patterns in all cases. Two siblings had similar symptoms indicating autosomai recessive inherited pattern. Pathologically, there was marked variation in fibre size and most small fibres were round. Some necrotic and regenerating fibers were seen. Fibres with centrally placed nuclei can be found frequently. No infiltrations of inflammatory cells were seen. Lobulated fibers were observed in 2 patients by NADH-TR stain. The expression of dystrophin, caveolin-3, α-, β-, γ- and δ-sarcoglycan protein were normally staining of 5 LGMD2A patients' specimens by immunohistochemistry. Two patients had reduced staining of dysferlin by immunohistochemistry study. Conclusions Clinical and pathological characteristics of our 5 LGMD2A patients are consistent with typical muscular dystrophy features reported in other countries. Identification of calpian-3 deletion by Western blot is essential for the diagnosis of calpainopathy. Key words: Muscular dystrophy, limb-girdle; Calpain; Muscle proteins; Immunohistochemistry; Blotting, western