title: Extensive morphological and immunohistochemical characterization in myotubular myopathy.
abstract: The X-linked myotubular myopathy (XLMTM) also called X-linked centronuclear myopathy is a rare congenital myopathy due to mutations in the MTM 1 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 MTM 1-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 MTM 1 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.
authors.affiliation: Unité de Morphologie Neuromusculaire, Institut de Myologie GHU La Pitié-Salpêtrière, Paris, France ; Department of Pediatrics, Tokyo Woman's Medical University Tokyo, Japan.
authors.forename: Minobu
authors.initials: M
authors.lastname: Shichiji
authors.affiliation: 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 ; Laboratoire Diagnostic Génétique, Faculté de Médecine - CHRU Strasbourg, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Biancalana
authors.affiliation: Unité de Morphologie Neuromusculaire, Institut de Myologie GHU La Pitié-Salpêtrière, Paris, France ; Groupe Hospitalier-Universitaire La Pitié-Salpêtrière, AP-HP, Centre de référence des maladies neuromusculaires Paris-Est, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Fardeau
authors.affiliation: UPMC-Paris6 UR76, INSERM UMR974, CNRS UMR 7215, Institut de Myologie GHU La Pitié-Salpêtrière, Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Hogrel
authors.affiliation: Department of Pediatrics, Tokyo Woman's Medical University Tokyo, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Osawa
authors.affiliation: 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.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Laporte
authors.affiliation: Unité de Morphologie Neuromusculaire, Institut de Myologie GHU La Pitié-Salpêtrière, Paris, France ; Groupe Hospitalier-Universitaire La Pitié-Salpêtrière, AP-HP, Centre de référence des maladies neuromusculaires Paris-Est, Paris, France ; UPMC-Paris6 UR76, INSERM UMR974, CNRS UMR 7215, Institut de Myologie GHU La Pitié-Salpêtrière, Paris, France.
authors.forename: Norma Beatriz
authors.initials: NB
authors.lastname: Romero
keywords: Centronuclear myopathies; MTM1; T-tubules; myotubular myopathy; myotubularin; satellite cells