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 language | English (US) |
|---|---|
| Pages (from-to) | 349-356 |
| Number of pages | 8 |
| Journal | Molecular Genetics and Metabolism |
| Volume | 100 |
| Issue number | 4 |
| DOIs | |
| State | Published - Aug 2010 |
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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
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 journal › Article
}
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 -