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

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

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).

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 4 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).

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).

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: Standard Poodle.

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

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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 Standard Poodle 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
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Reference


2008 Chen, X., Johnson, GS., Schnabel, RD., Taylor, JF., Johnson, GC., Parker, HG., Patterson, EE., Katz, ML., Awano, T., Khan, S., O'Brien, DP. :
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