Neuromuscular Disorders
Volume 17, Issue 7 , Pages 562-568, July 2007

Myofiber size correlates with MTM1 mutation type and outcome in X-linked myotubular myopathy

  • Christopher R. Pierson

      Affiliations

    • Department of Pathology, Division of Neuropathology, Children’s Hospital Boston and Brigham and Women’s Hospital, 300 Longwood Avenue, Boston, MA 02115, USA
    • Program in Genomics, Division of Genetics, Children’s Hospital Boston, 650 Enders, Boston, MA 02115, USA
    • Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA
    • Corresponding Author InformationCorresponding authors. Address: Program in Genomics, Division of Genetics, Children’s Hospital Boston, 650 Enders, Boston, MA 02115, USA. Tel.: +1 617 919 2170; fax: +1 617 730 0253.
    • ,
  • Pankaj B. Agrawal

      Affiliations

    • Program in Genomics, Division of Genetics, Children’s Hospital Boston, 650 Enders, Boston, MA 02115, USA
    • Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA
    • ,
  • Jessica Blasko

      Affiliations

    • Program in Genomics, Division of Genetics, Children’s Hospital Boston, 650 Enders, Boston, MA 02115, USA
    • ,
  • Alan H. Beggs

      Affiliations

    • Program in Genomics, Division of Genetics, Children’s Hospital Boston, 650 Enders, Boston, MA 02115, USA
    • Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA
    • Corresponding Author InformationCorresponding authors. Address: Program in Genomics, Division of Genetics, Children’s Hospital Boston, 650 Enders, Boston, MA 02115, USA. Tel.: +1 617 919 2170; fax: +1 617 730 0253.

Received 10 November 2006; received in revised form 13 March 2007; accepted 14 March 2007.

Abstract 

We aimed to correlate pathologic findings with MTM1 mutation type in a series of molecularly defined XLMTM cases. Clinical data from 15 XLMTM patients and their corresponding 16 muscle biopsies were studied. All patients were infants (range: 6–217 days old) when initially biopsied. The proportion of myofibers with central nuclei did not correlate with clinical outcome, however, morphometric studies showed that survivors had larger myofiber diameters in infancy than those who died (10.4±3.9μm versus 8.9±3μm; p<0.001). As a corollary, patients with MTM1 missense mutations had larger myofiber diameters (11.1±4μm), than those with truncation/deletion mutations (8.6±2.7μm) (controls 11.7±2.5μm) (p<0.0001). These data indicate that differences in myofiber size correlate with MTM1 mutation type and patient outcome. Failure to attain and/or maintain myofiber size, along with fiber type perturbations and the misplacement of myofiber nuclei and other organelles, are important components of XLMTM muscle pathology.

Keywords: Centronuclear myopathy, Morphometry, MTM1, Myotubularin, X-linked myotubular myopathy

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PII: S0960-8966(07)00111-3

doi:10.1016/j.nmd.2007.03.010

Refers to erratum:

  • Erratum to “Myofiber size correlates with MTM1 mutation type and outcome in X-linked myotubular myopathy” [Neuromuscular Disorders 17(7) (2007) 562–568]

    Christopher R. Pierson, Pankaj B. Agrawal, Jessica Blasko, Alan H. Beggs
    Neuromuscular Disorders June 2008 (Vol. 18, Issue 6, Page 519)

Neuromuscular Disorders
Volume 17, Issue 7 , Pages 562-568, July 2007

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