Studying the role of dystrophin-associated proteins in influencing Becker muscular dystrophy disease severity

Neuromuscul Disord. 2015 Mar;25(3):231-7. doi: 10.1016/j.nmd.2015.01.002. Epub 2015 Jan 14.

Abstract

Becker muscular dystrophy is characterized by a variable disease course. Many factors have been implicated to contribute to this diversity, among which the expression of several components of the dystrophin associated glycoprotein complex. Together with dystrophin, most of these proteins anchor the muscle fiber cytoskeleton to the extracellular matrix, thus protecting the muscle from contraction induced injury, while nNOS is primarily involved in inducing vasodilation during muscle contraction, enabling adequate muscle oxygenation. In the current study, we investigated the role of three components of the dystrophin associated glycoprotein complex (beta-dystroglycan, gamma-sarcoglycan and nNOS) and the dystrophin homologue utrophin on disease severity in Becker patients. Strength measurements, data about disease course and fresh muscle biopsies of the anterior tibial muscle were obtained from 24 Becker patients aged 19 to 66. The designation of Becker muscular dystrophy in this study was based on the mutation and not on the clinical severity. Contrary to previous studies, we were unable to find a relationship between expression of nNOS, beta-dystroglycan and gamma-sarcoglycan at the sarcolemma and disease severity, as measured by muscle strength in five muscle groups and age at reaching several disease milestones. Unexpectedly, we found an inverse correlation between utrophin expression at the sarcolemma and age at reaching disease milestones.

Keywords: Becker muscular dystrophy; Disease progression; Dystrophin associated glycoprotein complex; Utrophin; nNOS.

MeSH terms

  • Adult
  • Aged
  • Disease Progression
  • Dystroglycans / metabolism*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Middle Aged
  • Muscle Strength / physiology
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Muscular Dystrophy, Duchenne / diagnosis
  • Muscular Dystrophy, Duchenne / genetics
  • Muscular Dystrophy, Duchenne / pathology
  • Muscular Dystrophy, Duchenne / physiopathology*
  • Nitric Oxide Synthase Type I / metabolism*
  • Sarcoglycans / metabolism*
  • Sarcolemma / metabolism
  • Sarcolemma / pathology
  • Severity of Illness Index
  • Surveys and Questionnaires
  • Utrophin / metabolism*
  • Young Adult

Substances

  • DAG1 protein, human
  • Sarcoglycans
  • Utrophin
  • Dystroglycans
  • NOS1 protein, human
  • Nitric Oxide Synthase Type I