Résumé :
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Communication n° 422 Background: Mutations in myotilin gene have been described in two families with LGMD1A and, more recently in a subset of patients suffering from myofibrilar myopathy (MM). Objective: To describe the clinical, pathological, electrophysiological and genetic characteristics of a Spanish sporatic patient carrying a Ser55Phe mutation in the myotilin gene and contribute to define the phenotypic spectrum of myotilinopathies.. Patient/Methods: A 57-year-old Spanish woman with healthy nonconsanguineous parents had presented an involvement of skeletal (distal more than proximal, predominanly in lower extremities) muscles with onset at 42 years of age and with a rather severe progressivity leading soon to the bilateral foot drops. The achilian reflexes were abolished but she presented retraction of achilian tendons. Quadriceps muscles were spared. There was no involvement of cranial nerves, no signs of cardiac, hepatic or CNS involvement. Repeated serum CK levels were elevated 1 to 3-fold. None other family member presented neuromuscular diseases.The electrophysiological study showed myogenic patterns with abundant spontaneous activity. A diagnosis of MM or of sIBM was with spared quadriceps was discussed at the age of 55. Search for the molecular defect on GNE gene resulted negative. Results: Muscle (deltoid) biopsy showed myopathic changes, a few rimmed vacuoles, some focal inflammatory changes (CD3+) and focal myofibrillar destruction resulting in intracytoplasmic deposits strongly immunoreactive to myotilin antibody. MHC class I was not expressed. An abundant number of subsarcolemmal spheric inclusions of filamentous material with a mean diameter of 16 nm and a striking Z-line irregularity were found on electron microscopy. A molecular defect consisting in the myotilin Ser55Phe mutation, was found in the MYOT gene on chromosome 5q31 codifing for the myotilin. Conclusion: Myotilinopathy seems to be frequent among patients presenting MM of unknown genetic definite cause or atypical forms of IBM. To demonstrate the suggestive clinical and the myopathological data of myotilinopathy is mandatory before searching the molecular basis of the definite diagnosis.
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