A nonsense mutation in the acid α-glucosidase gene causes Pompe disease in Finnish and Swedish Lapphunds

PLoS One. 2013;8(2):e56825. doi: 10.1371/journal.pone.0056825. Epub 2013 Feb 14.

Abstract

Pompe disease is a recessively inherited and often fatal disorder caused by the deficiency of acid α-glucosidase, an enzyme encoded by the GAA gene and needed to break down glycogen in lysosomes. This glycogen storage disease type II has been reported also in Swedish Lapphund dogs. Here we describe the genetic defect in canine Pompe disease and show that three related breeds from Scandinavia carry the same mutation. The affected dogs are homozygous for the GAA c.2237G>A mutation leading to a premature stop codon at amino acid position 746. The corresponding mutation has previously been reported in humans and causes infantile Pompe disease in combination with a second fully deleterious mutation. The affected dogs from both the Finnish as well as the Swedish breed mimic infantile-onset Pompe disease genetically, but also clinico-pathologically. Therefore this canine model provides a valuable tool for preclinical studies aimed at the development of gene therapy in Pompe disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Codon, Nonsense*
  • Dogs
  • Female
  • Glycogen Storage Disease Type II / enzymology*
  • Glycogen Storage Disease Type II / genetics*
  • Male
  • Pedigree
  • Species Specificity
  • alpha-Glucosidases / genetics*

Substances

  • Codon, Nonsense
  • alpha-Glucosidases

Grants and funding

This study was funded by the Academy of Finland, the Sigrid Juselius Foundation and The Jane and Aatos Erkko Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.