Hereditary Ataxia Bobtail and Gordon Setter Type (HA)
Hereditary Ataxia Bobtail and Gordon Setter Type (HA) is a congenital neurodegenerative disorder occuring in Bobtail and Gordon Setter dog breed. Word ataxia has greek origin and it means ”without oder”. Hereditary ataxia is a heterogenious group of movement disorders. Within this group, forms of hereditary ataxia differ among each other in several ways, such as age of onset or mode of inheritance. They can be inherited as autosomal dominant, recessive or X linked trait. HA inherited as a dominant disorder is also known as spinocerebellar ataxia, or SCA. Until now, hereditary cerebellar degenerative disorders have been identified in over 20 breeds of dog and is most commonly inherited as an autosomal reccesive trait.
Cerebellum, also known as the ”little brain”, is a part of brain that has an important role in motor control, in way that it contributes to coordination, precision and accurate timing. One of the cells present in the cerebellum are the Purkinje cells or Purkinje neurons. Together, the Purkinje cells and the cerebellum have an essential role in the body’s motor function.
Characteristics and Symptoms
Hereditary ataxia is characterized by slow degeneration of the cerebellar cortex, with dramatic Purkinje neuron loss which results in a progressive gaint disfunction. Hereditary Ataxia Bobtail and Gordon Setter Type is an early onset disorder that is first noted in juvenile to young adult dogs, between ages of six months to four years. Common clinical signs that affected dogs develop are hypermetria, a truncal sway and intention tremor, and signs progress to cause severe gaint disturbances. Histopathological examination reveals loss of Purkinje cell, granule cell and molecular layer neurons, which causes atrophy of the cerebellar cortex.
Hereditary Ataxia Bobtail and Gordon Setter Type (HA) is linked to mutation in RAB24, gene encoding for GTPase Rab24 protein. This enzyme has an imortant role in membranous transport within the cell and cell division. It is highly expressed in the brain, unlike the rest of body where its expression is on low levels.
The disorder is inherited as an autosomal recessive disorder. Healthy parents of an affected puppy are obligate heterozygotes, and therefore carry one mutant allele. Heterozygotes have no symptoms. Dogs homozygous for the mutation will display the symptoms of the Hereditary Ataxia Bobtail and Gordon Setter Type (HA). At conception, when mating two carrier dogs, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Agler C, Nielsen DM, Urkasemsin G, Singleton A, Tonomura N, et al. (2014) Canine Hereditary Ataxia in Old English Sheepdogs and Gordon Setters Is Associated with a Defect in the Autophagy Gene Encoding RAB24. PLoS Genet 10(2): e1003991. doi:10.1371/journal.pgen.1003991.