Homozygous PPT1 Splice Donor Mutation in a Cane Corso Dog With Neuronal Ceroid Lipofuscinosis

A. Kolicheski, H. L. Barnes Heller, S. Arnold, R. D. Schnabel, J. F. Taylor, C. A. Knox, T. Mhlanga-Mutangadura, D. P. O'Brien, G. S. Johnson, J. Dreyfus, M. L. Katz

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)149-157
Number of pages9
JournalJournal of veterinary internal medicine
Issue number1
StatePublished - Jan 1 2017
Externally publishedYes

Bibliographical note

Funding Information:
We thank Candace Kassel and Cheryl Jensen for assistance in preparing samples for electron microscopy and immunohistochemistry. We also thank Cindy Cole from Mars Veterinary for providing us with DNA samples from members of the Cane Corso breed. Finally, the authors thank Dr Shahriar Salamat, from the University of Wisconsin Department of Pathology and Laboratory Medicine for his assistance with the initial diagnosis. Grant support: This work was supported in part by U.S. National Institutes of Health grant EY023968 (MLK) and Canine Health Foundation grant 02257 (GSJ) Conflict of Interest Declaration: Authors declare no conflict of interest. Off-label Antimicrobial Declaration: Authors declare no off-label use of antimicrobials.

Publisher Copyright:
Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.


  • Autofluorescence
  • CLN1 disease
  • Lysosomal storage disease
  • Molecular genetics
  • Whole genome sequence


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