Test Detail

Multidisease genetic panel for the Papillon / Continental Toy Spaniel bringing together five molecular tests: pap-PRA1 progressive retinal atrophy, factor VII deficiency (F7), neuroaxonal dystrophy (NAD), degenerative myelopathy (DM exon 2) and von Willebrand disease type 1 (vWD-1). Each condition has its own molecular basis and inheritance. The panel is complementary to ophthalmic, haemocoagulative and neurological examination in breeding selection.

Applicable breed: Papillon (and Phalène, a variety of the same breed). The pap-PRA1 CNGB1 variant was described in the breed (17.2 % carriers in a cohort of 145 Papillons/Phalènes). No systematic carrier frequency figures are published for F7, NAD, DM exon 2 or vWD-1 in the breed (limited data).

- Reduced night vision and progressive retinal atrophy (pap-PRA1)\n- Progressive blindness with abnormal fundus\n- Prolonged bleeding after surgery or trauma, ecchymoses and epistaxis (F7)\n- Mild to moderate mucosal bleeding (vWD-1)\n- Progressive ataxia, neurological signs and deterioration from a young age (NAD)\n- Progressive hindlimb paresis with proprioceptive ataxia (DM)

pap-PRA1 was described molecularly in 2013 as a frameshift mutation in CNGB1, with autosomal recessive inheritance and a median onset around 5.6 years. Canine factor VII deficiency was characterised in Beagle colonies (2006) and its F7 missense variant has been documented in more than 20 breeds, including the Papillon. Papillon neuroaxonal dystrophy was associated in 2017 with a missense variant of PLA2G6. Degenerative myelopathy was linked in 2009 to the SOD1 exon 2 variant (classic allele). von Willebrand disease type 1 is associated with variants of the VWF gene and its test must correspond to the breed variant.

- Genotype breeding animals before mating; the panel covers five conditions in a single sample.\n- Recessive (pap-PRA1, F7, NAD and DM exon 2): do not mate two carriers (25 % homozygotes per litter); carrier × clear produces no affected 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- For F7 and vWD-1, consider factor measurement before scheduled surgery in homozygotes and carriers.\n- For DM, homozygotes are not a breeding priority; mate carriers with clear animals.\n- After a confirmed clinical case, do not repeat the parental mating and communicate the status to the buyer.

pap-PRA1 is confirmed by ophthalmic examination and molecular testing; complementary annual examination (ECVO/CERF). Factor VII deficiency is confirmed by measurement of factor VII activity and molecular study; the differential diagnosis includes other coagulation defects and thrombocytopathies. vWD-1 is confirmed by measurement of von Willebrand factor antigen and activity. NAD is confirmed by histopathology (neuroaxonal spheroids) and molecular study; the differential diagnosis includes other neuroaxonal and degenerative dystrophies. DM is a diagnosis of exclusion: rule out spinal cord compression before attributing the picture to SOD1.

1. Winkler PA et al. 2013, modelo animal grande para la retinitis pigmentosa autosómica recesiva por CNGB1 (PLoS One) (PMID 23977260).
2. Ahonen SJ et al. 2013, mutación de cambio de marco en CNGB1 en Papillón y Phalène con atrofia progresiva de retina (PLoS One) (PMID 24015210).
3. Callan MB et al. 2006, nueva mutación missense causante de la deficiencia de factor VII en colonias de Beagle (J Thromb Haemost) (PMID 16961583).
4. Tsuboi M et al. 2017, identificación de la mutación missense PLA2G6 c.1579G>A en la distrofia neuroaxonal del Papillón (PLoS One) (PMID 28107443).
5. Awano T et al. 2009, análisis de asociación del genoma que revela una mutación de SOD1 en la mielopatía degenerativa canina (PNAS) (PMID 19188595).
6. Crespi JA et al. 2018, genotipificación y prevalencia de la mutación de vWD tipo 1 en Doberman Pinscher (J Vet Diagn Invest) (PMID 29271313).
7. OMIA:002723-9615, OMIA:000361-9615, OMIA:002105-9615, OMIA:001057-9615.