Muscular dystrophies due to glycosylation defects: diagnosis and therapeutic strategies

Curr Opin Neurol. 2011 Oct;24(5):437-42. doi: 10.1097/WCO.0b013e32834a95e3.

Abstract

Purpose of review: Dystroglycanopathies are a common group of diseases characterized by a reduction in α-dystroglycan glycosylation. This review discusses the recent novel discovery of additional dystroglycanopathy variants and progress in dystroglycanopathy animal models.

Recent findings: Several novel glycosyltransferase genes have been found to be responsible for a dystroglycanopathy phenotype, and in addition recessive mutations in DAG1 have been identified for the first time in a primary dystroglycanopathy. Studies in dystroglycanopathy mouse models have clarified some aspects of the structural defects observed in the central nervous system and in the eye, whereas a study in zebrafish implicates unfolded protein response in the pathogenesis of two of the secondary dystroglycanopathies.

Summary: Improved understanding of the molecular bases of dystroglycanopathies will lead to more precise diagnosis and genetic counseling; therapeutic strategies are being developed and tested in the preclinical models and it is hoped that these observations will pave the way to therapeutic interventions in humans.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dystroglycans / genetics
  • Dystroglycans / metabolism*
  • Glycosylation
  • Humans
  • Mice
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Muscular Dystrophies / genetics
  • Muscular Dystrophies / metabolism*
  • Muscular Dystrophies / therapy
  • Walker-Warburg Syndrome / genetics
  • Walker-Warburg Syndrome / metabolism*
  • Walker-Warburg Syndrome / therapy
  • Zebrafish

Substances

  • DAG1 protein, human
  • Muscle Proteins
  • Dystroglycans