title: SLC3A1 and SLC7A9 mutations in autosomal recessive or dominant canine cystinuria: a new classification system.
abstract: BACKGROUND
  Cystinuria, one of the first recognized inborn errors of metabolism, has been reported in many dog breeds.
  
  
  OBJECTIVE
  To determine urinary cystine concentrations, inheritance, and mutations in the SLC3A1 and SLC7A9 genes associated with cystinuria in 3 breeds.
  
  
  METHODS
  Mixed and purebred Labrador Retrievers (n = 6), Australian Cattle Dogs (6), Miniature Pinschers (4), and 1 mixed breed dog with cystine urolithiasis, relatives and control dogs.
  
  
  METHODS
  Urinary cystinuria and aminoaciduria was assessed and exons of the SLC3A1 and SLC7A9 genes were sequenced from genomic DNA.
  
  
  RESULTS
  In each breed, male and female dogs, independent of neuter status, were found to form calculi. A frameshift mutation in SLC3A1 (c.350delG) resulting in a premature stop codon was identified in autosomal-recessive (AR) cystinuria in Labrador Retrievers and mixed breed dogs. A 6 bp deletion (c.1095_1100del) removing 2 threonines in SLC3A1 was found in autosomal-dominant (AD) cystinuria with a more severe phenotype in homozygous than in heterozygous Australian Cattle Dogs. A missense mutation in SLC7A9 (c.964G>A) was discovered in AD cystinuria in Miniature Pinschers with only heterozygous affected dogs observed to date. Breed-specific DNA tests were developed, but the prevalence of each mutation remains unknown.
  
  
  CONCLUSIONS
  These studies describe the first AD inheritance and the first putative SLC7A9 mutation to cause cystinuria in dogs and expand our understanding of this phenotypically and genetically heterogeneous disease, leading to a new classification system for canine cystinuria and better therapeutic management and genetic control in these breeds.
authors.affiliation: Section of Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: A-K
authors.initials: AK
authors.lastname: Brons
authors.forename: P S
authors.initials: PS
authors.lastname: Henthorn
authors.forename: K
authors.initials: K
authors.lastname: Raj
authors.forename: C A
authors.initials: CA
authors.lastname: Fitzgerald
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: A C
authors.initials: AC
authors.lastname: Sewell
authors.forename: U
authors.initials: U
authors.lastname: Giger
mesh_terms: D026923:Amino Acid Transport Systems, Basic / Q000235:genetics*; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D003555:Cystinuria / Q000235:genetics / Q000652:urine / Q000662:veterinary*; D004247:DNA / Q000235:genetics; D004283:Dog Diseases / Q000235:genetics* / Q000652:urine; D004285:Dogs; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics; D016482:Urinalysis / Q000662:veterinary
chemical_list: D026923:Amino Acid Transport Systems, Basic; D026921:Amino Acid Transport Systems, Neutral; D004247:DNA
keywords: Hereditary disease; Metabolic disease; Nephropathy; Urolithiasis