Oculopharyngeal muscular dystrophy: a polyalanine myopathy

Curr Neurol Neurosci Rep. 2009 Jan;9(1):76-82. doi: 10.1007/s11910-009-0012-y.

Abstract

It has been 10 years since the identification of the first PABPN1 gene (GCN)(n)/polyalanine mutations responsible for oculopharyngeal muscular dystrophy (OPMD). These mutations have been found in most cases of OPMD diagnosed in more than 35 countries. Sequence analyses have shown that such mutations have occurred numerous times in human history. Although PABPN1 was found early on to be a component of the classic filamentous intranuclear inclusions (INIs), mRNA and other proteins also have been found to coaggregate in the INIs. It is still unclear if the INIs play a pathologic or a protective role. The generation of numerous cell and animal models of OPMD has led to greater insight into its complex molecular pathophysiology and identified the first candidate therapeutic molecules. This paper reviews basic and clinical research on OPMD, with special emphasis on recent developments in the understanding of its pathophysiology.

Publication types

  • Review

MeSH terms

  • Diagnosis, Differential
  • Genetic Counseling
  • Humans
  • Molecular Biology
  • Muscular Dystrophy, Oculopharyngeal* / genetics
  • Muscular Dystrophy, Oculopharyngeal* / pathology
  • Muscular Dystrophy, Oculopharyngeal* / physiopathology
  • Mutation
  • Peptides / genetics
  • Peptides / metabolism*
  • Poly(A)-Binding Protein I / genetics

Substances

  • Peptides
  • Poly(A)-Binding Protein I
  • polyalanine