Ataxia, cerebellar (SELENOP-related)

 

Gene: SELENOP (also called SEPP1)

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: Deletion, SELENOP gene (also called SEPP1 gene): 17.3Kb deletion of entire protein coding sequence, Chr.4.

Medical system: Neurological

Breed: Belgian Malinois

Age of onset of symptoms: 4 to 6 weeks

Ataxia (uncoordinated movements) is a common neurological sign seen in the dog that can be caused by environmental and/or genetic effects. Mutations in up to 30 different genes can be the cause of canine ataxia, with mutations that are quite specific to each breed affected.

Ataxia was diagnosed in a single litter of Belgian Shepherd dogs.  Clinical signs included problems with coordination and balance, muscle spasms and intention tremors. Symptoms ranged from mild balance problems to complete inability to move.  Histological examination of necropsy samples showed atrophy of cortical layers of the cerebellum with depletion of Purkinje cells.  Genomic sequencing of one affected animal revealed a homozygous 17.3 Kb deletion that removed the entire SELENOP gene.  The SELENOP gene codes for a selenium binding and transport protein.  Selenium is a trace element needed for the proper functioning of several antioxidant enzymes, such as within in the central nervous system.  However, selenium in high doses or non-regulated is toxic.  The observed deletion of the SELENOP gene co-segregated with the symptoms seen in the affected litter.  Furthermore, the mutation was found in a carrier (heterozygous) state in 38 out of 631 non-affected Belgian shepherd animals, to give a breed carrier frequency of 6%.  The mutation was not observed in 735 control genomes of dogs from other breeds.

A DNA test will now enable Belgian Malinois to test for this mutation, to help eliminate this disease from their breed.  Note however that the Belgian Malinois has additional causes of hereditary ataxia that have been characterized at the molecular level, including:

Spinocerebellar ataxia, early onset, with myokymia and seizures (KCNJ10-linked)

Spongy degeneration with cerebellar ataxia, SDCA2 (ATP1B2_linked)

Also, there are additional cases of hereditary ataxia in this breed whose cause has yet to be characterized.

 

References:

OMIA link: [2367-9615]

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

Christen M, Högler S, Kleiter M, et al. (2021) Deletion of the SELENOP gene leads to CNS atrophy with cerebellar ataxia in dogs. PLoS Genet 17:e1009716.   [pm/34339417]

 

With contributions by: Annabelle Séguin and Camille Davidson, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).