OMIA:002522-9615 : Ataxia, HACE1-related in Canis lupus familiaris
Categories: Nervous system phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 610876 (gene) , 616756 (trait)
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: 2022
Inheritance: Pedigree analysis of eight affected dogs from 5 litters suggested an autosomal recessive mode of inheritance (Bellamy et al., 2022)
Molecular basis: Bellamy et al. (2022): "Whole genome sequencing ... detected only four closely linked private variants at CFA12 ... . All four variants were located within HACE1 ... .Two of the variants were located in the 5’-region ... and the other two ... were located ...in exon 11 (ENSCAFT00000072236.1). [One variant] ... was an already annotated synonymous variant ... [and the likely causal variant] was a 1 bp deletion ... leading to a frameshift creating 33 new amino acids and a premature stop codon in exon 12."
Clinical features: Bellamy et al. (2022): "Owners reported an abnormal gait, especially in the pelvic limbs, of the affected dogs from around 4 weeks of age. The puppies were said to be unsteady, easily slipping on the floor with the pelvic limbs, occasionally falling over. In addition, they all had a hanging tail instead of the curled tail normal for this spitz breed. ... On neurological examination, the body posture was kyphotic with a broad-based pelvic limb stance. The gait was moderately ataxic with hypermetric tendencies, most prominent in the pelvic limbs."
Pathology: Bellamy et al. (2022): "No macroscopical abnormalities were observed .... In the cerebellum of all the examined cases, homogenous eosinophilic axonal swellings were present multifocally in the cerebellar granule cell layer ... . These structures stained positively for neurofilament by immunohistochemistry and immunofluorescence and were consistent with spheroids in the Purkinje cell axons (torpedoes) ... . Occasionally, the torpedoes were shrunken and surrounded by a vacuolated space. In the brain stem, vacuoles were found in a moderate number disseminated and multifocally, both in the white matter tracts and in neuronal nuclei close to neurons."
Breed: Norwegian Elkhound.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|HACE1||HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1||Canis lupus familiaris||12||NC_051816.1 (63187531..63079955)||HACE1||Homologene, Ensembl , NCBI gene|
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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|
|1421||Norwegian Elkhound||Ataxia, HACE1-related||HACE1||deletion, small (<=20)||Naturally occurring variant||CanFam3.1||12||g.62282767del||c.1001del||p.(G334Vfs*34)||ENSCAFT00000072236.1; ENSCAFP00000049888.1||2022||35061740|
|2022||Bellamy, K.K.L., Skedsmo, F.S., Hultman, J., Arnet, E.F., Guttersrud, O.A., Skogmo, H.K., Thoresen, S.I., Espenes, A., Jäderlund, K.H., Lingaas, F. :|
|A 1 bp deletion in HACE1 causes ataxia in Norwegian elkhound, black. PLoS One 17:e0261845, 2022. Pubmed reference: 35061740 . DOI: 10.1371/journal.pone.0261845.|
- Created by Imke Tammen2 on 29 Jan 2022