ATP13A2 missense variant in Australian Cattle Dogs with late onset neuronal ceroid lipofuscinosis.

Schmutz, Isabelle; Jagannathan, Vidya; Bartenschlager, Florian; Stein, Veronika M.; Gruber, Achim D; Leeb, Tosso; Katz, Martin L (2019). ATP13A2 missense variant in Australian Cattle Dogs with late onset neuronal ceroid lipofuscinosis. Molecular genetics and metabolism, 127(1), pp. 95-106. Elsevier 10.1016/j.ymgme.2018.11.015

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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.

Item Type:

Journal Article (Original Article)


05 Veterinary Medicine > Research Foci > NeuroCenter
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV) > DKV - Clinical Neurology
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics

UniBE Contributor:

Schmutz, Isabelle, Jagannathan, Vidya, Stein, Veronika Maria, Leeb, Tosso


500 Science > 590 Animals (Zoology)
600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health








Tosso Leeb

Date Deposited:

02 Sep 2019 13:36

Last Modified:

05 Dec 2022 15:30

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

Animal model CLN12 Canis lupus familiaris Dog Kufor-Rakeb syndrome Lysosomal storage disease Neurodegeneration Neuronal ceroid lipofuscinosis PARK9 Spastic paraplegia Whole genome sequencing




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