Extensive morphological and immunohistochemical characterization in myotubular myopathy

Brain and Behavior

Minobu Shichiji²  Valérie Biancalana³  Michel Fardeau²  Jean-Yves Hogrel⁴  Makiko Osawa¹  Jocelyn Laporte³ 

[1] Department of Pediatrics, Tokyo Woman's Medical University, Tokyo, Japan;Unité de Morphologie Neuromusculaire, Institut de Myologie, Paris, France;Department of Translational Medecine, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS, UMR7104, INSERM, U964, Collège de France, Université de Strasbourg, Illkirch, France;UPMC-Paris6 UR76, INSERM UMR974, CNRS UMR 7215, Institut de Myologie, Paris, France

关键词: Centronuclear myopathies;    MTM 1;    myotubular myopathy;    myotubularin;    satellite cells;    T‐tubules;   

DOI  :  10.1002/brb3.147

来源: Wiley

【 摘 要 】

Abstract

The X-linked myotubular myopathy (XLMTM) also called X-linked centronuclear myopathy is a rare congenital myopathy due to mutations in the MTM1 gene encoding myotubularin. The disease gives rise to a severe muscle weakness in males at birth. The main muscle morphological characteristics (significant number of small muscle fibers with centralized nuclei and type 1 fiber predominance) are usually documented, but the sequence of formation and maintenance of this particular morphological pattern has not been extensively characterized in humans. In this study, we perform a reevaluation of morphological changes in skeletal muscle biopsies in severe XLMTM. We correlate the pathologic features observed in the muscle biopsies of 15 newborns with MTM1-mutations according to the “adjusted-age” at the time of muscle biopsy, focusing on sequential analysis in the early period of the life (from 34 weeks of gestation to 3 months of age). We found a similar morphological pattern throughout the period analyzed; the proportion of myofibers with central nuclei was high in all muscle biopsies, independently of the muscle type, the age of the newborns at time of biopsy and the specific MTM1 mutation. We did not observe a period free of morphological abnormalities in human skeletal muscle as observed in myotubularin-deficient mouse models. In addition, this study demonstrated some features of delayed maturation of the muscle fibers without any increase in the number of satellite cells, associated with a marked disorganization of the muscle T-tubules and cytoskeletal network in the skeletal muscle fibers.

【 授权许可】

CC BY   
© 2013 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

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