Résumé :
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In myotonic dystrophy type 2 (DM2), CCUG expansions form pathogenic ribonuclear accumulations that are detectable by in situ hybridization (ISH). Clinical DM2 diagnosis is often overlooked due to a poorly specific presentation and a muscle biopsy showing a denervation-like pattern of unknown specificity, combining: (1) increased fibre size variation, (2) centronucleation, (3) small angulated fibres, (4) type 2 fibre atrophy, and (5) nuclear clumps. Here, we checked the presence of these alterations in a series of 2100 consecutive muscle biopsies in patients selected for unidentified myopathy with no inflammation or neuropathy. Then, we used automated [CCUG]8 ISH as a reference standard to evaluate the value of each histological feature for DM2 detection. Among 104 included patients, ISH identified 8 DM2+ and 96 DM2- cases. Multivariate analyses identified the combination of type 2 fibre atrophy and centronucleation as the most relevant (Se=1.0, Sp=0.92), whereas these changes were mutually exclusive in non-DM2 patients (p<0.0001). Relevance of the combination was confirmed in an additional independent series (15 DM2+ vs 17 DM2-). Further investigation uncovered that centronucleation selectively affects type 2 fibres in DM2, and, conversely, type 1 fibres in DM1 (p<0.0001). These results will facilitate the routine detection of DM2 and further substantiate a distinctive muscle pathophysiology, designating DM2 as a type 2 fibre myopathy.
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