OMIA 002092-9615 : Ataxia, spinocerebellar, SPTBN2-related in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 600224 , 615386 , 604985

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: unknown

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)

Breed: Beagle.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
SPTBN2 spectrin, beta, non-erythrocytic 2 Canis lupus familiaris 18 NC_006600.3 (50631053..50670428) SPTBN2 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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Beagle Ataxia, spinocerebellar, SPTBN2-related SPTBN2 deletion, small (<=20) p.G1952insRDRGQGRPLLLMHRHGAGAA 2012 22781464

Reference


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.

Edit History


  • Created by Tosso Leeb on 19 Jan 2017
  • Changed by Tosso Leeb on 02 Mar 2017
  • Changed by Tosso Leeb on 07 Jul 2017