title: Homozygous PPT1 Splice Donor Mutation in a Cane Corso Dog With Neuronal Ceroid Lipofuscinosis.
abstract: A 10-month-old spayed female Cane Corso dog was evaluated after a 2-month history of progressive blindness, ataxia, and lethargy. Neurologic examination abnormalities indicated a multifocal lesion with primarily cerebral and cerebellar signs. Clinical worsening resulted in humane euthanasia. On necropsy, there was marked astrogliosis throughout white matter tracts of the cerebrum, most prominently in the corpus callosum. In the cerebral cortex and midbrain, most neurons contained large amounts of autofluorescent storage material in the perinuclear area of the cells. Cerebellar storage material was present in the Purkinje cells, granular cell layer, and perinuclear regions of neurons in the deep nuclei. Neuronal ceroid lipofuscinosis (NCL) was diagnosed. Whole genome sequencing identified a PPT1c.124 + 1G>A splice donor mutation. This nonreference assembly allele was homozygous in the affected dog, has not previously been reported in dbSNP, and was absent from the whole genome sequences of 45 control dogs and 31 unaffected Cane Corsos. Our findings indicate a novel mutation causing the CLN1 form of NCL in a previously unreported dog breed. A canine model for CLN1 disease could provide an opportunity for therapeutic advancement, benefiting both humans and dogs with this disorder.
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, Columbia, MO.
authors.forename: A
authors.initials: A
authors.lastname: Kolicheski
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI.
authors.forename: H L
authors.initials: HL
authors.lastname: Barnes Heller
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI.
authors.forename: S
authors.initials: S
authors.lastname: Arnold
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: Mars Veterinary, Vancouver, WA.
authors.forename: C A
authors.initials: CA
authors.lastname: Knox
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 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: G S
authors.initials: GS
authors.lastname: Johnson
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI.
authors.forename: J
authors.initials: J
authors.lastname: Dreyfus
authors.affiliation: Mason Eye Institute, University of Missouri, Columbia, MO.
authors.forename: M L
authors.initials: ML
authors.lastname: Katz
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000175:diagnosis* / Q000235:genetics; D004285:Dogs; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D008279:Magnetic Resonance Imaging / Q000662:veterinary; D009472:Neuronal Ceroid-Lipofuscinoses / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics / Q000662:veterinary*
keywords: Autofluorescence; CLN1 disease; Lysosomal storage disease; Molecular genetics; Whole genome sequence