Résumé :
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Congenital myopathies are characterized by peculiar structural changes of muscular fibers. Recently, working on a series of cases close by their clinical and pathological features from the centronuclear myopathies, we identified a group of patients which presented a curious morphological pattern characterized by the presence of a variable amount of “dark necklace” fibers (DNF). Necklace fibers were found in both type1 and type2 fibers. They showed a basophilic subsarcolemmal ring deposit, few micrometers apart from the plasma membrane. The ring stained intensively with HE, GT, NADH-TR, SDH and COX, but was not detected on the myofibrillar ATPase. Occasional nuclei align with the necklace. EM analysis showed that the necklace was situated about 3µm from the sarcolemma. It consists of normally oriented and disorganized myofibrils with remarkably small diameter, surrounded by increased, normally structured mitochondria and numerous sarcotubular profiles. Immunohistochemical studies showed an intense labeling using anti-SERCA1 and SERCA2 antibodies, but not with other proteins of the sarcoplasmic reticulum (calsequestrin, ryanodine receptor, triadin), and the T-tubule (dihydropyridine receptor-alpha1subunit). In addition, there was a marked reaction with anti-desmin and aB-crystallin antibodies, but not for myotilin antibodies. Clinically, the four cases identified were sporadic. Symptoms began in the first decade, as a slowly progressive proximal pattern of weakness predominantly in lower limbs. No facial or extraocular muscle involvement was observed. Serum CK were slightly elevated in two cases and normal in the two others. Electromyography showed unspecific myopathic changes in all of them, in one case nerve conduction studies showed distal slowing of latencies. The peculiar structural alterations were not present in any other cases of centronuclear myopathies. Preliminary molecular genetics analysis allowed to exclude DNM2 and BIN genes. MTM gene study is in progress. The mechanism of this structural defect in myofibrillar organization and organelle positioning remains to be elucidated.
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