Golden Retriever dogs with neuronal ceroid lipofuscinosis have a two-base-pair deletion and frameshift in CLN5.
We studied a recessive, progressive neurodegenerative disease occurring in Golden Retriever siblings with an onset of signs at 15 months of age. As the disease progressed these signs included ataxia, anxiety, pacing and circling, tremors, aggression, visual impairment and localized and generalized seizures. A whole genome sequence, generated with DNA from one affected dog, contained a plausibly causal homozygous mutation: CLN5:c.934_935delAG. This mutation was predicted to produce a frameshift and premature termination codon and encode a protein variant, CLN5:p.E312Vfs*6, which would lack 39 C-terminal amino acids. Eighteen DNA samples from the Golden Retriever family members were genotyped at CLN5:c.934_935delAG. Three clinically affected dogs were homozygous for the deletion allele; whereas, the clinically normal family members were either heterozygotes (n = 11) or homozygous for the reference allele (n = 4). Among archived Golden Retrievers DNA samples with incomplete clinical records that were also genotyped at the CLN5:c.934_935delAG variant, 1053 of 1062 were homozygous for the reference allele, 8 were heterozygotes and one was a deletion-allele homozygote. When contacted, the owner of this homozygote indicated that their dog had been euthanized because of a neurologic disease that progressed similarly to that of the affected Golden Retriever siblings. We have collected and stored semen from a heterozygous Golden Retriever, thereby preserving an opportunity for us or others to establish a colony of CLN5-deficient dogs.
Department of Veterinary Pathobiology, University of Missouri-Columbia, Columbia, MO, USA. Electronic address: dhg27f@mail.missouri.edu.
D
D
Gilliam
Department of Veterinary Pathobiology, University of Missouri-Columbia, Columbia, MO, USA. Electronic address: akv22@mail.missouri.edu.
A
A
Kolicheski
Department of Veterinary Pathobiology, University of Missouri-Columbia, Columbia, MO, USA. Electronic address: johnsongs@missouri.edu.
G S
GS
Johnson
Department of Veterinary Pathobiology, University of Missouri-Columbia, Columbia, MO, USA. Electronic address: tendai@missouri.edu.
T
T
Mhlanga-Mutangadura
Division of Animal Science, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, MO, USA. Electronic address: taylorjerr@missouri.edu.
J F
JF
Taylor
Division of Animal Science, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, MO, USA. Electronic address: schnabelr@missouri.edu.
R D
RD
Schnabel
Mason Eye Institute, School of Medicine, University of Missouri, Columbia, MO, USA. Electronic address: katzm@health.missouri.edu.
M L
ML
Katz
D000818:Animals; D001483:Base Sequence; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D016368:Frameshift Mutation; D006720:Homozygote; D008565:Membrane Proteins / Q000235:genetics*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics / Q000662:veterinary*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion
D008565:Membrane Proteins
Batten disease; CLN5 mutation; Canine model; Lysosomal storage disease; Neurodegeneration; Neuronal ceroid lipofuscinosis; Whole genome sequence