Sensory neuropathy: A DNA test can detect the genetic mutation in Border Collies

Sensory neuropathy (or progressive axonopathy) is a rare neurological disease that primarily affects Border Collies. It worsens over time, and its prognosis is poor, especially since there is no treatment. However, British researchers have successfully identified the mutation responsible for the condition in this breed and developed a DNA test to screen for it.   The disease appears in young Border Collies between the ages of two and seven months. Affected dogs gradually lose the sensation of pain in their limbs due to the degeneration of sensory and motor nerve cells. Clinical signs include joint deformities, self-inflicted lesions from licking and biting due to the lack of pain sensitivity, and progressive ataxia. Euthanasia is often unavoidable. To help owners and breeders of the breed combat this debilitating condition, the Kennel Club Genetics Center at the Animal Health Trust (AHT) investigated the genetic basis of the disease in Border Collies using three DNA samples from three affected dogs. The three samples were compared to DNA from 170 Border Collies already included in the AHT’s database as part of its research on epilepsy in this breed. Using this DNA database, the researchers were able to quickly identify the chromosome containing the genetic mutation for sensory neuropathy and sequenced it to isolate the defective gene responsible for the disease. Once the mutation was detected, AHT scientists collaborated with veterinarians from the universities of Glasgow and Missouri to test the DNA of eleven dogs with sensory neuropathy. All of the animals were found to carry two copies of the identified mutation (each inherited from one parent). This discovery should help reduce the number of puppies carrying this disease in the future. To this end, Border Collie breeders are encouraged to use the new DNA test to help take the next step: eradicating this condition from the breed. Although rare, cases have been reported worldwide (United Kingdom, United States, Belgium, Japan, Italy), and until a case is detected, it is impossible to know which bloodline contains asymptomatic carriers (one copy of the normal gene and one copy of the mutant gene). They will not develop the disease, but will pass on the sensory neuropathy gene to, on average, 75% of their offspring (25% of the puppies will develop the disease and 50% will themselves be asymptomatic carriers). To make DNA testing more affordable for owners and breeders, the AHT has developed another screening test that combines, in addition to sensory neuropathy, two other conditions affecting Border Collies: neutrophil sequestration syndrome and vitamin B12 deficiency. Dogs affected by neutrophil sequestration syndrome suffer from an immune system deficiency due to a decrease in the number of circulating neutrophils and must be euthanized at a young age. Vitamin B12 deficiency, or Imerslund-Gräsbeck syndrome, is another disease that affects the blood and the nervous system, leading to growth retardation and even anemia. All three conditions require two copies of the defective gene for a dog to be affected. Tests conducted on a random selection of DNA samples from Border Collies revealed that 6% were carriers of neutrophil sequestration syndrome and 8% were carriers of vitamin B12 deficiency.  

About Sensory Neuropathy

The primary clinical signs of the disease include, on the one hand, locomotor disorders such as moderate ataxia and, on the other hand, signs related to the loss of pain sensation: self-inflicted wounds, particularly on the limbs (and sometimes in other areas, such as the genital region) accompanied by erythema, ulcerations, perionyxis, loss of claws, subluxation, painless fractures, osteomyelitis, and/or self-amputation. In affected animals, proprioceptive deficits (often more severe in the hind limbs), diminished or absent spinal reflexes, and even urinary incontinence and regurgitation are observed. Given their severely impaired quality of life, these dogs are generally euthanized for welfare reasons before the age of two.