title: A missense mutation in canine CLN6 in an Australian shepherd with neuronal ceroid lipofuscinosis.
abstract: The childhood neuronal ceroid lipofuscinoses (NCLs) are inherited neurodegenerative diseases that are progressive and ultimately fatal. An Australian Shepherd that exhibited a progressive neurological disorder with signs similar to human NCL was evaluated. The cerebral cortex, cerebellum, and retina were found to contain massive accumulations of autofluorescent inclusions characteristic of the NCLs. Nucleotide sequence analysis of DNA from the affected dog identified a T to C variant (c.829T>C) in exon 7 of CLN6. Mutations in the human ortholog underlie a late-infantile form of NCL in humans. The T-to-C transition results in a tryptophan to arginine amino acid change in the predicted protein sequence. Tryptophans occur at homologous positions in the CLN6 proteins from all 13 other vertebrates evaluated. The c.829T>C transition is a strong candidate for the causative mutation in this NCL-affected dog. Dogs with this mutation could serve as a model for the analogous human disorder.
authors.affiliation: Mason Eye Institute, School of Medicine, College of Veterinary Medicine, University of Missouri, One Hospital Drive, Columbia, MO 65212, USA. katzm@health.missouri.edu
authors.forename: Martin L
authors.initials: ML
authors.lastname: Katz
authors.forename: Fabiana H
authors.initials: FH
authors.lastname: Farias
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Sanders
authors.forename: Rong
authors.initials: R
authors.lastname: Zeng
authors.forename: Shahnawaz
authors.initials: S
authors.lastname: Khan
authors.forename: Gary S
authors.initials: GS
authors.lastname: Johnson
authors.forename: Dennis P
authors.initials: DP
authors.lastname: O'Brien
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001315:Australia; D002531:Cerebellum / Q000473:pathology / Q000648:ultrastructure; D004252:DNA Mutational Analysis; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005091:Exons / Q000235:genetics; D045888:Ganglion Cysts / Q000473:pathology; D006720:Homozygote; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics / Q000662:veterinary*
chemical_list: D008565:Membrane Proteins