dc.contributor.author
Schmutz, Isabelle
dc.contributor.author
Jagannathan, Vidhya
dc.contributor.author
Bartenschlager, Florian
dc.contributor.author
Stein, Veronika M.
dc.contributor.author
Gruber, Achim D.
dc.contributor.author
Leeb, Tosso
dc.contributor.author
Katz, Martin L.
dc.date.accessioned
2019-07-10T09:37:17Z
dc.date.available
2019-07-10T09:37:17Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/25001
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-2758
dc.description.abstract
The neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage disorders characterized by progressive neurodegeneration and declines in neurological functions. Pathogenic sequence variants in at least 13 genes underlie different forms of NCL, almost all of which are recessively inherited. To date 13 sequence variants in 8 canine orthologs of human NCL genes have been found to occur in 11 dog breeds in which they result in progressive neurological disorders similar to human NCLs. Canine NCLs can serve as models for preclinical evaluation of therapeutic interventions for these disorders. In most NCLs, the onset of neurological signs occurs in childhood, but some forms have adult onsets. Among these is CLN12 disease, also known as Kufor-Rakeb syndrome, PARK9, and spastic paraplegia78. These disorders result from variants in ATP13A2 which encodes a putative transmembrane ion transporter important for lysosomal function. Three Australian Cattle Dogs (a female and two of her offspring) were identified with a progressive neurological disorder with an onset of clinical signs at approximately 6 years of age. The affected dogs exhibited clinical courses and histopathology characteristic of the NCLs. Whole genome sequence analysis of one of these dogs revealed a homozygous c.1118C > T variant in ATP13A2 that predicts a nonconservative p.(Thr373Ile) amino acid substitution. All 3 affected dogs were homozygous for this variant, which was heterozygous in 42 of 394 unaffected Australian Cattle Dogs, the remainder of which were homozygous for the c.1118C allele. The high frequency of the mutant allele in this breed suggests that further screening for this variant should identify additional homozygous dogs and indicates that it would be advisable to perform such screening prior to breeding Australian Cattle Dogs.
en
dc.format.extent
12 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject
canis lupus familiaris
en
dc.subject
animal model
en
dc.subject
whole genome sequencing
en
dc.subject
neuronal ceroid lipofuscinosis
en
dc.subject
lysosomal storage disease
en
dc.subject
neurodegeneration
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::616 Krankheiten
dc.subject.ddc
500 Naturwissenschaften und Mathematik::590 Tiere (Zoologie)::599 Mammalia (Säugetiere)
dc.title
ATP13A2 missense variant in Australian Cattle Dogs with late onset neuronal ceroid lipofuscinosis
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1016/j.ymgme.2018.11.015
dcterms.bibliographicCitation.journaltitle
Molecular Genetics and Metabolism
dcterms.bibliographicCitation.number
1
dcterms.bibliographicCitation.volume
127
dcterms.bibliographicCitation.url
https://doi.org/10.1016/j.ymgme.2018.11.015
refubium.affiliation
Veterinärmedizin
refubium.affiliation.other
Institut für Tierpathologie
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.issn
1096-7192