A mutation in canine PPT1 causes early onset neuronal ceroid lipofuscinosis in a Dachshund

Douglas N. Sanders, Fabiana H. Farias, Gary S. Johnson, Vivian Chiang, James R. Cook, Dennis P. O'Brien, Sandra L. Hofmann, Jui Yun Lu, Martin L. Katz

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


The neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage diseases characterized by progressive neurodegeneration and accumulation of autofluorescent storage granules. A 9-month-old Miniature Dachshund presented with NCL-like signs that included disorientation, ataxia, weakness, visual impairment, and behavioral changes. Neurons throughout the CNS contained autofluorescent lysosomal inclusions with granular osmiophilic deposit (GROD) ultrastructure characteristic of classical infantile NCL (INCL). Human INCL is an autosomal recessive disorder that results from mutations in PPT1, a gene that encodes the enzyme palmitoyl protein thioesterase 1 (PPT1; EC 3.1.22). Resequencing of PPT1 from the affected dog revealed that the dog was homozygous for a single nucleotide insertion in exon 8 (PPT1 c.736_737insC), upstream from the His289 active site. Brain tissue from this dog lacked PPT1 activity. The sire and dam of the propositus were heterozygous for the c.736_737insC mutation; whereas, 127 unrelated Dachshunds were homozygous for the wild-type allele. This is the first reported instance of canine NCL caused by a mutation in PPT1.

Original languageEnglish (US)
Pages (from-to)349-356
Number of pages8
JournalMolecular genetics and metabolism
Issue number4
StatePublished - Aug 2010


  • Canine model
  • INCL
  • Lysosomal storage disease
  • Neurodegeneration
  • Palmitoyl protein thioesterase

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology


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