Multi-disease genetic panel for the Caniche bringing together five molecular tests: two forms of progressive retinal atrophy (rcd4-PRA and prcd-PRA), neonatal encephalopathy with seizures (NEWS), von Willebrand disease type 1 (vWD-1) and degenerative myelopathy (DM exon 2). Each condition has its own molecular basis and inheritance. The panel is complementary to the ocular examination and to neurological/haematological follow-up in breeding selection.

Applicable breed: Caniche (the different sizes share several variants). NEWS is described in the giant Caniche (Standard poodle), with the variant widespread in the breed according to the initial characterisation studies. No reliable carrier-frequency figures are available for rcd4-PRA, prcd-PRA, vWD-1 and DM exon 2 in the breeding population (limited data).

- Reduced night vision and progressive retinal atrophy (rcd4-PRA and prcd-PRA)\n- Progressive blindness with altered ocular fundus\n- Seizures and neurological deterioration in the neonatal puppy (NEWS)\n- Early death in most cases (NEWS)\n- Prolonged bleeding after surgery or trauma, ecchymoses and epistaxis (vWD-1)\n- Progressive paresis of the hind limbs with ataxia (DM)

prcd-PRA was associated with the PRCD gene. rcd4-PRA is associated with variants of C2orf71/PCARE, the same family that causes late-onset PRA in other breeds (Downs et al. 2013). Neonatal encephalopathy with seizures of the giant Caniche (NEWS) was associated with a missense variant of ATF2 (Chen et al. 2008). von Willebrand disease type 1 is associated with variants of the VWF gene. Degenerative myelopathy was linked in 2009 to the exon 2 variant of SOD1.

- Genotype breeding dogs before mating; the panel covers five conditions in a single sample.\n- Recessive (rcd4-PRA, prcd-PRA, NEWS and DM exon 2): do not cross two carriers (25% homozygotes per litter); carrier × clear does not produce affected animals.\n- DM exon 2: homozygotes are not a breeding priority because of their incomplete penetrance; cross carriers with clear animals.\n- vWD-1 is dominant with incomplete penetrance: a carrier can transmit the variant to ~50% of the offspring; consider mating with a clear animal.\n- In vWD-1, assess von Willebrand factor dosing before scheduled surgery in homozygotes and carriers.\n- After a confirmed clinical case, do not repeat the parental cross and communicate the status to the buyer.

The two PRAs of the panel are differentiated by age of onset and ocular fundus, but molecular diagnosis is what confirms the suspicion. Complementary annual ocular examination (ECVO/CERF). NEWS must be differentiated from other neonatal encephalopathies (infectious, metabolic, toxic). vWD-1 is confirmed by antigen and activity dosing of von Willebrand factor; the differential diagnosis includes other coagulation defects and thrombocytopathies. DM is a diagnosis of exclusion: rule out spinal compression before attributing the picture to SOD1.

1. Zangerl B et al. 2006, mutación idéntica en un gen retiniano novel que causa prcd en perros (Genomics) (PMID 16938425).
2. Downs LM et al. 2013, PRA de inicio tardío en Gordon e Irish Setter asociada a una mutación de cambio de marco en C2orf71 (Anim Genet) (PMID 22686255).
3. Chen X et al. 2008, encefalopatía neonatal con convulsiones en Caniche estándar y mutación missense del ortólogo canino de ATF2 (Neurogenetics) (PMID 18074159).
4. Awano T et al. 2009, mutación de SOD1 en la mielopatía degenerativa canina (PNAS) (PMID 19188595).
5. Crespi JA et al. 2018, genotipificación y prevalencia de la mutación de vWD tipo 1 en Doberman Pinscher (J Vet Diagn Invest) (PMID 29271313).
6. OMIA:001057-9615.