Résumé :
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Introduction. An autosomal dominant vacuolar myopathy (ADVM) linked to 19p13.3 (OMIM 601846) has been recently described in two large Italian families. It is characterized by adult onset, variable muscle weakness with distal to proximal progression, dysphonia and dysphagia, arreflexia, mixed neuropathic and myopathic EMG changes and numerous “rimmed vacuoles” in muscle biopsies. Patients and methods. We present a Spanish family with five affected members in two consecutive generations. Age at onset was variable, with distal weakness and amyotrophy, and further extension to upper limbs. In four patients a muscle biopsy was performed under informed consent. Techniques included acetylcholinesterase, acid phosphatase, alizarin red, and immunohistochemistry for Dystrophin, DRP2, LAMP2, Tau, B-amyloid, ubiquitin and C5b9. Ultrastructural examination was performed. DNA from 6 members of the family (4 clinically affected and 2 asymptomatic) was extracted from peripheral lymphocytes and linkage analysis was performed to 19p13 using microsatellite markers. Results. Muscle biopsy findings were similar in the four biopsied individuals. There was a dystrophic pattern of variable intensity with striking and numerous autophagic vacuoles located at the periphery of muscle fibers or centrally. Acid phosphatase activity was increased, abnormal calcium deposits were abundant and acetylcholinesterase stain disclosed an abnormal pattern with fine deposits all over the vacuoles. Ubiquitin was positive within the vacuoles. Tau, B-amyloid and PrP were negative. LAMP2 was positive. Electron microscopy showed numerous autophagic vacuoles with membranous and multilamellar bodies and myelin figures, some of which were membrane-bound. Linkage analysis showed co-segregation in the critical region 19p13.3 previously described. Summary and conclusions This is the first Spanish family with ADVM linked to 19p13.3. Muscle pathology is somehow distinctive among the large group of vacuolar myopathies, with particular immunohistochemical findings. This myopathy could be more frequent than expected. We are searching for a candidate gene, related to the lysosomal degradation pathway.
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