Cerebellar cortical degeneration, SNX14-related

 

Gene: SNX14

Transmission: Autosomal, recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, SNX14 gene (splicing error); c.2653 + 1 G >A, exon26, chromosome 12.

Breed: Vizsla

Medical system: Neurologic

Age of onset of symptoms: By 3 months.

Ataxia in dogs is a general clinical diagnosis and can have both environmental and genetic causes.  Mutations in several genes can be the cause of hereditary cerebellar cortical degeneration, resulting in a progressive ataxia that varies in breed occurrence, age of onset, and rate of progression.

Two Hungarian Vizsla puppies from the same litter were presented for progressive ataxia first observed at 3 months of age.  Clinical signs included lack of coordinated movements (dysmetria), exaggerated movements (hypermetria), intention tremors, difficulty walking, and muscle weakness.  A diagnosis of cerebellar ataxia was made, and due to the progressive nature and poor prognosis of the disease, the dogs were euthanized.  Histological examination of the cerebellum confirmed degeneration of the cortex with loss of Purkinje cells.  DNA analysis identified a homozygote splice variant mutation within the SNX14 gene as the suggested genetic cause of the disease.  Screening of 133 unrelated Vizsla dogs for the mutation revealed a carrier frequency of 2.3% in the wider breed population.  This disease and mutation should be of concern to veterinarians and to Vizsla breeders.  DNA testing should be performed on Vizsla dogs to be used for reproduction to identify carriers and to eliminate the disease from the breed by selective breeding.

Characterized gene mutations resulting in cerebellar cortical degeneration in dogs include:

ATP1B2 gene, Spongy degeneration, cerebellar ataxia. OMIA link: [2110-9615]

CAPN1 gene, Spinocerebellar ataxia, late onset. OMIA link: [1820-9615]

GRM1 gene, Neonatal ataxia (Bandera’s disease. OMIA link: [0078-9615]

ITPR1 gene, Ataxia, spinocerebellar. OMIA link: [2097-9615]

KCNJ10 gene, Spinocerebellar ataxia, early onset. OMIA link: [2089-9615]

RAB24 gene, Cerebellar ataxia, juvenile onset. OMIA link: [1913-9615]

SEL1L gene, Cerebellar ataxia, early-onset.  OMIA link: [1692-9615]

SPTBN2 gene, Neonatal cerebellar cortical degeneration.  OMIA link: [2092-9615]

SNX14 gene, Cerebellar cortical degeneration.  OMIA link: [2034-9615]

 

References:

OMIA link: [2034-9615]

Cocostîrc V, Paștiu AI, Pusta DL. (2023) An overview of canine inherited neurological disorders with known causal variants. Animals (Basel) 13:3568. [pm/38003185]

Stee K, Van Poucke M, Lowrie M, et al. (2023) Phenotypic and genetic aspects of hereditary ataxia in dogs. J Vet Intern Med 37:1306-1322. [pm/37341581]

Fenn J, Boursnell M, Hitti RJ, et al. (2016) Genome sequencing reveals a splice donor site mutation in the SNX14 gene associated with a novel cerebellar cortical degeneration in the Hungarian Vizsla dog breed. BMC Genet 17:123.  [pm/27566131]

 

Contributed by: Adam Nachate and Nelson Coto Mendoza, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS)