OMIA:002092-9615 : Ataxia, spinocerebellar, SPTBN2-related in Canis lupus familiaris
Categories: Nervous system phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 600224 (trait) , 615386 (trait) , 604985 (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: 2012
Species-specific name: Neonatal cerebellar cortical degeneration
Species-specific description: Ataxia is characterized by uncoordinated movements and represents a relatively non-specific clinical sign. This entry describes an ataxia form that is caused by a genetic variant in the SPTBN2 gene. Phenotypically related ataxias in dogs may also be caused by variants in the ATP1B2, CAPN1, GRM1, ITPR1, KCNJ10, RAB24, SNX14, and SEL1L genes. Thus locus heterogeneity for this phenotype must be considered. The SPTBN2 associated canine disorder represents a model for spinocerebeallar ataxia, autosomal recessive 14, and possibly also spiocerebellar ataxia 5 in humans (see MIM links above).
Molecular basis: In the first published success of genome-wide RNA sequencing (mRNA-seq) in domestic animals, Forman et al. (2012) sequenced the mRNA from the cerebellum of one affected dog. The canine sequence data were compared with sequence of 27 human genes in which mutations have caused similar clinical signs in humans, and which have canine homologues. One of the canine homologues, SPTBN2, turned out to have an 8bp deletion which segregates perfectly with the canine disease. The deletion is in exon 29 "is predicted to result in a run of 27 aberrant amino acids, followed by premature termination with a 410 amino acid truncation p.G1952insRDRGQGRPLLLMHRHGAGAACQEPLCS*"
Clinical features: A (single) four- week- old male beagle puppy with a ten-day history of severe cerebellar ataxia was investigated. "The dog was the only affected one from a litter of seven puppies. The breeder noticed that the affected puppy was not able to ambulate normally from the onset of walking and the clinical signs had remained stable since then. The puppy was otherwise eating and drinking well and there were no signs of systemic illness in the littermates, in the dam (also during gestation) or in the sire. Physical examination did not reveal any gross abnormalities apart from the neurological signs. Neurological examination revealed severe cerebellar ataxia, with tendency to lean and fall towards both sides, resulting in inability to walk without assistance. Proprioceptive positioning was normal while hopping reactions were abnormal with delayed onset of protraction and exaggerated response, once initiated. Spinal reflexes were normal in all four limbs. Cranial nerve examination revealed an absent menace response bilaterally with normal vision. Occasionally when the head was positioned in extension spontaneous rotatory nystagmus was observed. A lesion involving mainly the cerebellum and spinocerebellar tracts was suspected." (Forman et al. 2012)
Pathology: "Histopathologically, the lesions were confined to the cerebellum. Examination of serial cerebellar sections of the four week old puppy identified mild loss of Purkinje cells, with corresponding increased numbers of astrocytes. Moderate numbers of Purkinje cells were shrunken with angular cell margins, hypereosinophilic cytoplasm, and condensed nuclei (Figure 1A). Occasional associated swollen dendritic processes were identified. Spheroids were rarely seen. Mild spongiosis was present at the granular cell layer – Purkinje cell interface Bielschowsky fiber stain was performed and demonstrated the subacute loss of Purkinje cells, also called “empty baskets” " (Forman et al. 2012)
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|SPTBN2||spectrin, beta, non-erythrocytic 2||Canis lupus familiaris||18||NC_051822.1 (51662893..51701379)||SPTBN2||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|
|457||Beagle||Ataxia, spinocerebellar, SPTBN2-related||SPTBN2||deletion, small (<=20)||Naturally occurring variant||CanFam3.1||18||g.50666027_50666034del||c.5855_5862del||p.(I1952Rfs*28)||XM_005631422.3; XP_005631479.1; published as chr18:53,691,704_53,691,711del (CanFam2); p.(G1952insRDRGQGRPLLLMHRHGAGAA); coordinates in the table have been updated to a recent reference genome and / or transcript and are updated to HGVS nomenclature||2012||22781464|
|2012||Forman, O.P., De Risio, L., Stewart, J., Mellersh, C.S., Beltran, E. :|
|Genome-wide mRNA sequencing of a single canine cerebellar cortical degeneration case leads to the identification of a disease associated SPTBN2 mutation. BMC Genet 13:55, 2012. Pubmed reference: 22781464 . DOI: 10.1186/1471-2156-13-55.|
- Created by Tosso Leeb on 19 Jan 2017
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