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 journalArticle

41 Citations (Scopus)

Abstract

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
Volume100
Issue number4
DOIs
StatePublished - Aug 2010

Fingerprint

Ceroid
Neuronal Ceroid-Lipofuscinoses
Canidae
Mutation
Dogs
Lysosomal Storage Diseases
Vision Disorders
Ataxia
Dams
Neurons
Exons
Brain
Catalytic Domain
Deposits
Nucleotides
Genes
Alleles
Tissue
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Sanders, D. N., Farias, F. H., Johnson, G. S., Chiang, V., Cook, J. R., O'Brien, D. P., ... Katz, M. L. (2010). A mutation in canine PPT1 causes early onset neuronal ceroid lipofuscinosis in a Dachshund. Molecular Genetics and Metabolism, 100(4), 349-356. https://doi.org/10.1016/j.ymgme.2010.04.009

A mutation in canine PPT1 causes early onset neuronal ceroid lipofuscinosis in a Dachshund. / Sanders, Douglas N.; Farias, Fabiana H.; Johnson, Gary S.; Chiang, Vivian; Cook, James R.; O'Brien, Dennis P.; Hofmann, Sandra L.; Lu, Jui Yun; Katz, Martin L.

In: Molecular Genetics and Metabolism, Vol. 100, No. 4, 08.2010, p. 349-356.

Research output: Contribution to journalArticle

Sanders, DN, Farias, FH, Johnson, GS, Chiang, V, Cook, JR, O'Brien, DP, Hofmann, SL, Lu, JY & Katz, ML 2010, 'A mutation in canine PPT1 causes early onset neuronal ceroid lipofuscinosis in a Dachshund', Molecular Genetics and Metabolism, vol. 100, no. 4, pp. 349-356. https://doi.org/10.1016/j.ymgme.2010.04.009
Sanders, Douglas N. ; Farias, Fabiana H. ; Johnson, Gary S. ; Chiang, Vivian ; Cook, James R. ; O'Brien, Dennis P. ; Hofmann, Sandra L. ; Lu, Jui Yun ; Katz, Martin L. / A mutation in canine PPT1 causes early onset neuronal ceroid lipofuscinosis in a Dachshund. In: Molecular Genetics and Metabolism. 2010 ; Vol. 100, No. 4. pp. 349-356.
@article{a4d4ee5a5f9d4f0f924025980d275243,
title = "A mutation in canine PPT1 causes early onset neuronal ceroid lipofuscinosis in a Dachshund",
abstract = "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.",
keywords = "Canine model, INCL, Lysosomal storage disease, Neurodegeneration, Palmitoyl protein thioesterase",
author = "Sanders, {Douglas N.} and Farias, {Fabiana H.} and Johnson, {Gary S.} and Vivian Chiang and Cook, {James R.} and O'Brien, {Dennis P.} and Hofmann, {Sandra L.} and Lu, {Jui Yun} and Katz, {Martin L.}",
year = "2010",
month = "8",
doi = "10.1016/j.ymgme.2010.04.009",
language = "English (US)",
volume = "100",
pages = "349--356",
journal = "Molecular Genetics and Metabolism",
issn = "1096-7192",
publisher = "Academic Press Inc.",
number = "4",

}

TY - JOUR

T1 - A mutation in canine PPT1 causes early onset neuronal ceroid lipofuscinosis in a Dachshund

AU - Sanders, Douglas N.

AU - Farias, Fabiana H.

AU - Johnson, Gary S.

AU - Chiang, Vivian

AU - Cook, James R.

AU - O'Brien, Dennis P.

AU - Hofmann, Sandra L.

AU - Lu, Jui Yun

AU - Katz, Martin L.

PY - 2010/8

Y1 - 2010/8

N2 - 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.

AB - 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.

KW - Canine model

KW - INCL

KW - Lysosomal storage disease

KW - Neurodegeneration

KW - Palmitoyl protein thioesterase

UR - http://www.scopus.com/inward/record.url?scp=77954660164&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954660164&partnerID=8YFLogxK

U2 - 10.1016/j.ymgme.2010.04.009

DO - 10.1016/j.ymgme.2010.04.009

M3 - Article

VL - 100

SP - 349

EP - 356

JO - Molecular Genetics and Metabolism

JF - Molecular Genetics and Metabolism

SN - 1096-7192

IS - 4

ER -