Test Detail

Multidisease genetic panel for the Dobermann grouping five molecular tests: degenerative myelopathy (DM exon 2), narcolepsy, von Willebrand disease type 1 (vWD-1) and two colour loci — B-locus (brown/chocolate/liver, TYRP1) and D-locus (dilution, MLPH). The panel combines three clinical conditions (DM and narcolepsy recessive; vWD-1 dominant with incomplete penetrance) with two coat markers useful for breeding. The molecular test is complementary —not a substitute— to neurological examination and haemostatic study in breeding selection.

Applicable breed: Dobermann. vWD-1 is frequent in the breed (relevant allele frequency in population studies; Crespi et al., 2018). The HCRTR2 narcolepsy variant has a lower case load and DM exon 2 is present in lines; the SOD1 variant is pan-breed. Reliable country-specific frequencies for the breeding population are not published systematically (limited data; see Donner et al., 2023).

- Excessive daytime sleepiness and cataplexy (loss of muscle tone with emotion) (narcolepsy)\n- REM sleep attacks during the day\n- Prolonged bleeding after surgery or trauma, ecchymoses and epistaxis (vWD-1)\n- Pale mucous membranes from occasional haemorrhage\n- Progressive hindlimb paresis with proprioceptive ataxia (DM)\n- Brown/liver coat colour (B-locus) and blue/isabella (D-locus) — they are not disease

Canine narcolepsy in the Dobermann was one of the first genetic sleep disorders characterised in the species and was associated with a SINE insertion in intron 3 of the hypocretin/orexin receptor type 2 gene (HCRTR2), a natural model of human narcolepsy (Lin et al., 1999). Canine von Willebrand disease type 1 was associated with a variant of the VWF gene and is especially frequent in the Dobermann (Crespi et al., 2018). Canine DM was linked to the SOD1 exon 2 variant (Awano et al., 2009). The B (TYRP1) and D (MLPH) colour loci are classic in canine coat genetics and are used to predict brown pigment and dilution (blue/isabella).

- Genotype breeding animals before mating; the panel covers five conditions and markers in a single sample\n- For DM and narcolepsy (recessive): do not mate two carriers — 25 % risk of affected homozygotes; carrier × clear is safe if the offspring is tested\n- For vWD-1 (dominant with incomplete penetrance): consider mating carriers with clear animals; measure von Willebrand factor before scheduled surgery\n- For B-locus and D-locus: they guide coat colour prediction; they do not imply disease\n- For DM: mutated homozygotes are not a breeding priority\n- After a confirmed clinical case, do not repeat the parental mating and communicate the status to the buyer

Narcolepsy is confirmed by polysomnography and molecular testing; the differential diagnosis includes other causes of sleepiness and cataplexy (neurological, metabolic, pharmacological). vWD-1 is confirmed by measurement of von Willebrand factor antigen and activity; the differential diagnosis includes other coagulation defects and thrombocytopathies. DM is a diagnosis of exclusion: rule out spinal cord compression and disc herniation before attributing the picture to SOD1. Colour dilution alopecia can occur in dogs with MLPH dilution and is not a disease independent of the marker.

1. Lin L, et al. The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell. 1999. PMID: 10458611.
2. Crespi JA, et al. von Willebrand disease type 1 in Doberman Pinscher dogs: genotyping and prevalence of the mutation in the Buenos Aires region, Argentina. J Vet Diagn Invest. 2018. PMID: 29271313.
3. Awano T, et al. PNAS. 2009. PMID: 19188595.
4. Schmutz SM, et al. TYRP1 and MC1R genotypes and their effects on coat color in dogs. Mamm Genome. 2002. PMID: 12140685.
5. Drögemüller C, et al. A noncoding MLPH SNP at the splice donor of exon 1 represents a candidate causal mutation for coat color dilution in dogs. J Hered. 2007. PMID: 17519392.
OMIA:000263-9615 (DM); OMIA:000703-9615 (narcolepsia); OMIA:001057-9615 (vWD1); OMIA:001249-9615 (B-locus/TYRP1); OMIA:000031-9615 (D-locus/MLPH).