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A truncating mutation in ATP13A2 is responsible for adult-onset neuronal ceroid lipofuscinosis in Tibetan terriers
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2011 (English)In: Neurobiology of Disease, ISSN 0969-9961, E-ISSN 1095-953X, Vol. 42, no 3, 468-474 p.Article in journal (Refereed) Published
Abstract [en]

A recessive, adult-onset neuronal ceroid-lipofuscinosis (NCL) occurs in Tibetan terriers. A genome-wide association study restricted this NCL locus to a 1.3 Mb region of canine chromosome 2 which contains canine ATP13A2. NCL-affected dogs were homozygous for a single-base deletion in ATP13A2, predicted to produce a frameshift and premature termination codon. Homozygous truncating mutations in human ATP13A2 have been shown by others to cause Kufor-Rakeb syndrome (KRS), a rare neurodegenerative disease. These findings suggest that KRS is also an NCL, although analysis of KRS brain tissue will be needed to confirm this prediction. Generalized brain atrophy, behavioral changes, and cognitive decline occur in both people and dogs with ATP13A2 mutations: however, other clinical features differ between the species. For example, Tibetan terriers with NCL develop cerebellar ataxia not reported in KRS patients and KRS patients exhibit parkinsonism and pyramidal dysfunction not observed in affected Tibetan terriers. To see if ATP13A2 mutations could be responsible for some cases of human adult-onset NCL (Kufs disease), we resequenced ATP13A2 from 28 Kufs disease patients. None of these patients had ATP13A2 sequence variants likely to be causal for their disease, suggesting that mutations in this gene are not common causes of Kufs disease.

Place, publisher, year, edition, pages
2011. Vol. 42, no 3, 468-474 p.
Keyword [en]
ATP13A2, Kufs disease, PARK9, Kufor-Rakeb syndrome, Parkinson's disease, Dog, Neurodegeneration
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-153567DOI: 10.1016/j.nbd.2011.02.009ISI: 000290081700026PubMedID: 21362476OAI: oai:DiVA.org:uu-153567DiVA: diva2:417198
Available from: 2011-05-16 Created: 2011-05-16 Last updated: 2011-06-28Bibliographically approved

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Lindblad-Toh, Kerstin
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Department of Medical Biochemistry and Microbiology
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