title: A L2HGDH initiator methionine codon mutation in a Yorkshire terrier with L-2-hydroxyglutaric aciduria.
abstract: BACKGROUND
  L-2-hydroxyglutaric aciduria is a metabolic repair deficiency characterized by elevated levels of L-2-hydroxyglutaric acid in urine, blood and cerebrospinal fluid. Neurological signs associated with the disease in humans and dogs include seizures, ataxia and dementia.
  
  
  METHODS
  Here we describe an 8 month old Yorkshire terrier that presented with episodes of hyperactivity and aggressive behavior. Between episodes, the dog's behavior and neurologic examinations were normal. A T2 weighted MRI of the brain showed diffuse grey matter hyperintensity and a urine metabolite screen showed elevated 2-hydroxyglutaric acid. We sequenced all 10 exons and intron-exon borders of L2HGDH from the affected dog and identified a homozygous A to G transition in the initiator methionine codon. The first inframe methionine is at p.M183 which is past the mitochondrial targeting domain of the protein. Initiation of translation at p.M183 would encode an N-terminal truncated protein unlikely to be functional.
  
  
  CONCLUSIONS
  We have identified a mutation in the initiation codon of L2HGDH that is likely to result in a non-functional gene. The Yorkshire terrier could serve as an animal model to understand the pathogenesis of L-2-hydroxyglutaric aciduria and to evaluate potential therapies.
authors: Department of Veterinary Pathobiology, University of Missouri, Columbia, USA. fhfdpd@mail.missouri.edu
authors: Fabiana H G
authors: FH
authors: Farias
authors: Rong
authors: R
authors: Zeng
authors: Gary S
authors: GS
authors: Johnson
authors: G D
authors: GD
authors: Shelton
authors: Dominique
authors: D
authors: Paquette
authors: Dennis P
authors: DP
authors: O'Brien
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D020739:Brain Diseases, Metabolic, Inborn / Q000235:genetics / Q000378:metabolism / Q000662:veterinary*; D004283:Dog Diseases / Q000235:genetics* / Q000473:pathology; D004285:Dogs; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D009154:Mutation
chemical_list: D000429:Alcohol Oxidoreductases