Résumé :
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Communication n° 557. X-linked myotubular myopathy (XLMTM) is due to MTM1 mutations; the gene product is known as myotubularin. Muscle biopsy shows a high proportion of hypotrophic myofibers with centrally placed nuclei. Most of our knowledge of XLMTM muscle pathology is derived from reports describing individuals or families. A morphologic study of a series of patients with documented MTM1 mutations would enhance our understanding of XLMTM. To meet this need, clinical diagnostic muscle biopsy material, including histochemical slides and electron microscopical material was collected from 10 patients with known MTM1 mutations. Histochemical preparations were available in 10 cases and a paraffin embedded block was available from 1 case. Seven cases had material available from ultrastructural studies. Most patients (8/10) were biopsied in the first year of life and one patient was biopsied twice. MTM1 mutations include: 3 patients with missense mutations, 4 patients with deletions, and a splicing mutation in 1 patient. All biopsies showed marked variation in myofiber size. Morphometery on H&E stained frozen sections revealed that patients with MTM1 mutations responsible for myotubularin truncations tend to have smaller myofibers (median 9.1 microns) than those with missense mutations (median 11.2 microns) (p=0.055). The median percent of myofibers with central nuclei ranged from 6.3% to 30.9% and did not correlated with MTM1 mutation (p=0.6). The patient who was biopsied twice (at 8 days and 3.3 years of age) showed increasing central nuclei (median of 19% to 30% per high power field) and a trend toward decreasing myofiber size (14.9Æ3.8 to 12Æ6.4 microns) over time. Electron microscopic findings include, focal myofibrillar disarray (6/7), irregularly contoured nuclei (7/7) and abundant, misplaced glycogen that occupied the thin filaments (7/7) and appeared juxtaposed to the Z-line (2/7), and misplaced mitochondria (7/7). The pathologic findings in human XLMTM muscle are in keeping with a deficit in myofiber maintenance encountered in the mtm1 knockout mouse.
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