title: Australian Cattle Dogs with Neuronal Ceroid Lipofuscinosis are Homozygous for a CLN5 Nonsense Mutation Previously Identified in Border Collies.
abstract: BACKGROUND
  Neuronal ceroid lipofuscinosis (NCL), a fatal neurodegenerative disease, has been diagnosed in young adult Australian Cattle Dogs.
  
  
  OBJECTIVE
  Characterize the Australian Cattle Dog form of NCL and determine its molecular genetic cause.
  
  
  METHODS
  Tissues from 4 Australian Cattle Dogs with NCL-like signs and buccal swabs from both parents of a fifth affected breed member. Archived DNA samples from 712 individual dogs were genotyped.
  
  
  METHODS
  Tissues were examined by fluorescence, electron, and immunohistochemical microscopy. A whole-genome sequence was generated for 1 affected dog. A TaqMan allelic discrimination assay was used for genotyping.
  
  
  RESULTS
  The accumulation of autofluorescent cytoplasmic storage material with characteristic ultrastructure in tissues from the 4 affected dogs supported a diagnosis of NCL. The whole-genome sequence contained a homozygous nonsense mutation: CLN5:c.619C>T. All 4 DNA samples from clinically affected dogs tested homozygous for the variant allele. Both parents of the fifth affected dog were heterozygotes. Archived DNA samples from 346 Australian Cattle Dogs, 188 Border Collies, and 177 dogs of other breeds were homozygous for the reference allele. One archived Australian Cattle Dog sample was from a heterozygote.
  
  
  CONCLUSIONS
  The homozygous CLN5 nonsense is almost certainly causal because the same mutation previously had been reported to cause a similar form of NCL in Border Collies. Identification of the molecular genetic cause of Australian Cattle Dog NCL will allow the use of DNA tests to confirm the diagnosis of NCL in this breed.
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, Columbia, MO.
authors.forename: A
authors.initials: A
authors.lastname: Kolicheski
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, Columbia, MO.
authors.forename: G S
authors.initials: GS
authors.lastname: Johnson
authors.affiliation: Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO.
authors.forename: D P
authors.initials: DP
authors.lastname: O'Brien
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, Columbia, MO.
authors.forename: T
authors.initials: T
authors.lastname: Mhlanga-Mutangadura
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, Columbia, MO.
authors.forename: D
authors.initials: D
authors.lastname: Gilliam
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, Columbia, MO.
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, Columbia, MO.
authors.forename: T D
authors.initials: TD
authors.lastname: Anderson-Sieg
authors.affiliation: Division of Animal Sciences and Informatics Institute, University of Missouri, Columbia, MO.
authors.forename: R D
authors.initials: RD
authors.lastname: Schnabel
authors.affiliation: Division of Animal Sciences, University of Missouri, Columbia, MO.
authors.forename: J F
authors.initials: JF
authors.lastname: Taylor
authors.affiliation: Animal Medical Center of New York, New York, NY.
authors.forename: A
authors.initials: A
authors.lastname: Lebowitz
authors.affiliation: Animal Medical Center of New York, New York, NY.
authors.forename: B
authors.initials: B
authors.lastname: Swanson
authors.affiliation: Blue Pearl Veterinary Hospital, Tacoma, WA.
authors.forename: D
authors.initials: D
authors.lastname: Hicks
authors.affiliation: Chicago Veterinary Specialty Group, Chicago, IL.
authors.forename: Z E
authors.initials: ZE
authors.lastname: Niman
authors.affiliation: Veterinary Specialty Services Neurology Department, Manchester, MO.
authors.forename: F A
authors.initials: FA
authors.lastname: Wininger
authors.affiliation: Veterinary Specialty Services Neurology Department, Manchester, MO.
authors.forename: M C
authors.initials: MC
authors.lastname: Carpentier
authors.affiliation: Mason Eye Institute, University of Missouri, Columbia, MO.
authors.forename: M L
authors.initials: ML
authors.lastname: Katz
mesh_terms: D000818:Animals; D018389:Codon, Nonsense; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005260:Female; D020022:Genetic Predisposition to Disease; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics / Q000662:veterinary*; D010375:Pedigree
chemical_list: D018389:Codon, Nonsense; D008565:Membrane Proteins
keywords: Autofluorescence; Lysosomal storage disease; Molecular genetics; Whole-genome sequence