OMIA:001471-9615 : Neonatal encephalopathy with seizures in Canis lupus familiaris (dog)

Categories: Nervous system phene

Possibly relevant human trait(s) and/or gene(s) (MIM number): 123811 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2008

Species-specific symbol: NEWS

Species-specific description: The disorder is characterized by pups that are small at birth, fail to nurse or thrive, then develop neurological signs and usually die by 7 weeks of age. A genetic test is available.

Mapping: The locus for NEWS was mapped by linkage analysis with microsatellites in a large family with 20 affected dogs. Maximum LOD scores exceeding 7 were obtained on CFA36 between markers UMC0297 and REN252E18 (Chen et al., 2008). The ATF2 gene was identified as a positional and functional candidate gene within the 2.87 Mb critical interval.

Molecular basis: The causative variant is a missense c.152T>G transversion causing a p.M51R methionine to arginine substitution in ATF2 (Chen et al., 2008). The mutation lies in a hydrophobic docking site for protein kinases that activate ATF2. Mutant ATF2 retains partial activity (Chen et al., 2008).

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Clinical features: Affected puppies are small at birth and do not develop normally. They initially nurse poorly, but begin nursing sufficiently after several days (Chen et al., 2008). At approximately 3 weeks of age, weakness, ataxia, whole-body tremors, wide-based stance with increased extensor tone, and axial muscle weakness with neck ventroflexion is observed. Affected pups do not interact with the dam or littermates and have slow responses to external stimuli (Chen et al., 2008). At approximately 3 to 6 weeks of age, affected puppies develop generalized clonic-tonic seizures that quickly become refractory to treatment. They become laterally recumbent with extensor rigidity and opisthotonus, and usually die or are euthanized before 7 weeks of age (Chen et al., 2008; Yu et al. 2020).

Pathology: The cerebellum is smaller than normal and contains dysplastic foci of cells from the granular layer intermixed with those from the Purkinje layer (Chen et al., 2008). Yu et al. (2020): "Magnetic resonance imaging showed reduced whole-brain size, dilated ventricles, developmental abnormalities of the white matter of the cerebrum, white matter signal abnormalities in the occipital lobe, and abnormal morphology of the cerebellum. Histopathology included previously unrecognized irregular neuronal migration in the subventricular zone around the lateral ventricles in the frontal lobe and white matter rarefaction especially at the level of the occipital lobe in the cerebrum ..,."

Prevalence: Of 1038 standard poodles genotyped, 36% were carriers and 2.7% were affected (Chen et al., 2008).

Control: Relatives of affected pups should be tested to identify carriers. Matings of carriers is discouraged, although breeding them to noncarriers will avoid production of affected pups.

Genetic testing: A test is available.

Breed: Poodle, Standard (Dog) (VBO_0201056).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ATF2 activating transcription factor 2 Canis lupus familiaris 36 NC_051840.1 (19255411..19170174) ATF2 Homologene, Ensembl , NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
65 Poodle, Standard (Dog) Neonatal encephalopathy with seizures ATF2 missense Naturally occurring variant CanFam3.1 36 g.19078954A>C c.152T>G p.(M51R) 2008 18074159 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2022). OMIA:001471-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

References

Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2020 Yu, Y., Hasegawa, D., Chambers, J.K., Kojima, K., Asada, R., Johnson, G.S., Uchida, K. :
Magnetic resonance imaging and histopathologic findings from a standard poodle with neonatal encephalopathy with seizures. Front Vet Sci 7:578936, 2020. Pubmed reference: 33244473. DOI: 10.3389/fvets.2020.578936.
2008 Chen, X., Johnson, G.S., Schnabel, R.D., Taylor, J.F., Johnson, G.C., Parker, H.G., Patterson, E.E., Katz, M.L., Awano, T., Khan, S., O'Brien, D.P. :
A neonatal encephalopathy with seizures in standard poodle dogs with a missense mutation in the canine ortholog of ATF2. Neurogenetics 9:41-9, 2008. Pubmed reference: 18074159. DOI: 10.1007/s10048-007-0112-2.

Edit History


  • Created by Frank Nicholas on 12 Jul 2009
  • Changed by Vicki Meyers-Wallen on 18 Sep 2011
  • Changed by Frank Nicholas on 28 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Tosso Leeb on 29 May 2013
  • Changed by Imke Tammen2 on 22 May 2022