Dogs with N/N genotype do not have the Doberman Pinscher narcolepsy variant.
Dogs with N/DN genotype are carriers of Doberman Pinscher narcolepsy. If two carriers are mated, 25% of the offspring in the litter are expected to be affected and another 50% of the offspring are expected to be carriers.
Dogs with DN/DN genotype will display symptoms of narcolepsy.
Narcolepsy is a chronic sleep disorder characterized by an inability to remain awake or alert for extended periods during normal waking hours or especially after stimulation. A narcoleptic episode often involves collapse into a sleeping episode that ends abruptly, and then the dog resumes normal activity. Affected dogs may not completely fall asleep but may just be unalert. Affected dogs typically show signs between 4 and 6 months of age. However, symptoms can occur as early as 1 month and do not seem to progress after 1 year.
In Doberman Pinschers, an insertion of 226 bp in hypocretin receptor 2gene (HCRTR2: c.647 -35ins226) has been identified as the causal mutation. This gene is involved in cell signaling that enables normal regulation of sleep and wakefulness. This insertion is predicted to alter the normal gene product (protein) by disrupting the last 50% of the protein.
In Doberman Pinschers, the disease is inherited in an autosomal recessive fashion, meaning two copies must be present for the disease to manifest, and both sexes are affected equally.
Recommendations on testing: Testing for narcolepsy can assist veterinarians with diagnosis. This test is specifically recommended for Doberman Pinschers, particularly those related to affected dogs, as test results can assist in identifying carriers among breeding stock to select appropriate mates that will reduce the risk of producing affected offspring. Breeding two carriers is predicted to produce litters with 25% of the pups being affected. Breeding affected dogs or carriers to each other is not recommended.
Note: This test is specific for the autosomal recessive mutation present in the Doberman Pinscher.
Normal. Dog does not carry the Doberman narcolepsy associated variant.
Carrier. Dog has one copy of the Doberman narcolepsy associated variant.
Affected. Dog has two copies of the Doberman narcolepsy associated variant and will develop symptoms of narcolepsy.
Lin, L., Faraco, J., Li, R., Kadotani, H., Rogers, W., Lin, X., Qiu, X., de Jong, P.J., Nishino, S., & Mignot, E. (1999). The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell, 98(3), 365-376. doi: 10.1016/s0092-8674(00)81965-0
Hungs, M., Fan, J., Lin, L., Lin, X., Maki, R.A., & Mignot, E. (2001). Identification and functional analysis of mutations in the hypocretin (orexin) genes of narcoleptic canines. Genome Research, 11(4), 531-539. doi: 10.1101/gr.gr-1610r