Peer-reviewed veterinary case report
SPTBN2 gene mutation found in Beagle with cerebellar degeneration
By Forman, Oliver P et al.·Published in BMC genetics·2012·Kennel Club Genetics Centre, United Kingdom·View original on PubMed →
PetCaseFinder translated the abstract of this peer-reviewed paper into plain English so pet owners can read it. We do not publish original research — every detail traces back to the citation above. How we work →
Original publication title: Genome-wide mRNA sequencing of a single canine cerebellar cortical degeneration case leads to the identification of a disease associated SPTBN2 mutation.
- Species:
- dog
Plain-English summary
A 4-week-old Beagle was unable to walk properly and showed signs of progressive coordination problems, leading the owner to make the difficult decision to euthanize. A tissue examination revealed that the dog had a condition called neonatal cerebellar cortical degeneration, which is linked to the loss of specific brain cells. Genetic testing identified a mutation in the SPTBN2 gene, which is important for brain cell development. This mutation was found to be associated with the dog's neurological issues, confirming a genetic cause for the condition. Unfortunately, the dog did not recover due to the severity of the disease.
People also search for: Beagle coordination problems · puppy cerebellar degeneration · SPTBN2 mutation in dogs · neonatal cerebellar ataxia in Beagles
Abstract
BACKGROUND: Neonatal cerebellar cortical degeneration is a neurodegenerative disease described in several canine breeds including the Beagle. Affected Beagles are unable to ambulate normally from the onset of walking and the main pathological findings include Purkinje cell loss with swollen dendritic processes. Previous reports suggest an autosomal recessive mode of inheritance. The development of massively parallel sequencing techniques has presented the opportunity to investigate individual clinical cases using genome-wide sequencing approaches. We used genome-wide mRNA sequencing (mRNA-seq) of cerebellum tissue from a single Beagle with neonatal cerebellar cortical degeneration as a method of candidate gene sequencing, with the aim of identifying the causal mutation. RESULTS: A four-week old Beagle dog presented with progressive signs of cerebellar ataxia and the owner elected euthanasia. Histopathology revealed findings consistent with cerebellar cortical degeneration. Genome-wide mRNA sequencing (mRNA-seq) of RNA from cerebellum tissue was used as a method of candidate gene sequencing. After analysis of the canine orthologues of human spinocerebellar ataxia associated genes, we identified a homozygous 8 bp deletion in the β-III spectrin gene, SPTBN2, associated with spinocerebellar type 5 in humans. Genotype analysis of the sire, dam, ten clinically unaffected siblings, and an affected sibling from a previous litter, showed the mutation to fully segregate with the disorder. Previous studies have shown that β-III spectrin is critical for Purkinje cell development, and the absence of this protein can lead to cell damage through excitotoxicity, consistent with the observed Purkinje cell loss, degeneration of dendritic processes and associated neurological dysfunction in this Beagle. CONCLUSIONS: An 8 bp deletion in the SPTBN2 gene encoding β-III spectrin is associated with neonatal cerebellar cortical degeneration in Beagle dogs. This study shows that mRNA-seq is a feasible method of screening candidate genes for mutations associated with rare diseases when a suitable tissue resource is available.
Find similar cases for your pet
PetCaseFinder finds other peer-reviewed reports of pets with the same symptoms, plus a plain-English summary of what was tried across them.
Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/22781464/