Test Detail

Multidisease genetic panel for the Chihuahua that brings together four molecular tests for ocular and neurological conditions: prcd progressive retinal atrophy (prcd-PRA), cone-rod retinal degeneration due to RPGRIP1 (historically cord1 and registered in OMIA as cone-rod dystrophy 4, crd4), the oligogenic modifier MAP9 (~22 kb deletion that worsens the degeneration caused by RPGRIP1) and Lafora disease (progressive myoclonic epilepsy). The panel is complementary to, not a substitute for, ocular examination and neurological follow-up in breeding selection.

Applicable breed: Chihuahua. Lafora disease is documented in the breed (Barrientos 2019, PMID 30525203). The RPGRIP1 and MAP9 variants are common in subsets of breeds that barely overlap and only exceed a frequency of 0.05 in the long-haired miniature dachshund; their validation in the Chihuahua is not established (limited data). prcd-PRA is described in small breeds, including the long-haired Chihuahua. There are no reliable carrier frequencies in the breeding population.

- Genotype breeding animals with the panel before mating\n- prcd-PRA, crd-PRA/cord1 and Lafora (recessive): do not mate two carriers (25% of homozygotes affected); carrier x clear is acceptable if the offspring intended for breeding are tested\n- MAP9: interpret the combined RPGRIP1 + MAP9 genotype, never in isolation; do not discard animals based on the MAP9 result alone\n- RPGRIP1/MAP9: not validated in the Chihuahua (frequency > 0.05 only in the long-haired miniature dachshund); do not use their results for breeding culling in this breed\n- Lafora: exclude affected animals from breeding and avoid spreading the allele to lines where it is not present\n- After a confirmed clinical case, do not repeat the parental mating and communicate the status to the buyer

The interpretation of crd-PRA risk depends on the combined RPGRIP1/MAP9 genotype; MAP9 is a modifier and does not equate to blindness. Bear in mind that crd1 corresponds to PDE6B (terriers) and that part of the literature uses crd4 for the C2orf71/PCARE form of the Gordon/Irish setter: do not confuse the entities. Annual ocular examination (ECVO/CERF) and electroretinography when appropriate. Lafora disease is confirmed by molecular testing; myoclonus induced by sensory stimuli is characteristic; the differential includes other genetic and toxic epilepsies.

1. prcd-PRA: Zangerl B et al. 2006. Identical mutation in a novel retinal gene causes progressive rod-cone degeneration. Genomics. PMID: 16938425; Goldstein O et al. 2006. Linkage disequilibrium mapping in domestic dog breeds. Genomics. PMID: 16859891
2. crd-PRA/cord1 (RPGRIP1): Mellersh CS et al. 2006. Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds. Genomics. PMID: 16806805; OMIA:001432-9615 (Retinal atrophy - Cone-rod dystrophy 4; símbolos cord1/crd4)
3. MAP9 modificador: Miyadera K et al. 2012. Genome-wide association study in RPGRIP1(-/-) dogs identifies a modifier locus. Mamm Genome. PMID: 22193413; Forman OP et al. 2016. Canine genome assembly correction facilitates identification of a MAP9 deletion as a potential age of onset modifier. Mamm Genome. PMID: 27017229; Das RG et al. 2017. Variabilities in retinal function and structure in a canine model of cone-rod dystrophy. Sci Rep. PMID: 28993665; Ripolles-Garcia A et al. 2023. Natural disease history of a canine model of oligogenic RPGRIP1-cone-rod dystrophy. Hum Mol Genet. PMID: 36951959; Donner J & Mellersh C. 2024. Frequency of RPGRIP1 and MAP9 genetic modifiers of canine progressive retinal atrophy, in 132 breeds. Anim Genet. PMID: 38752391
4. Nomenclatura crd1/crd4: Goldstein O et al. 2013. IQCB1 and PDE6B mutations cause similar early onset retinal degenerations. Invest Ophthalmol Vis Sci. PMID: 24045995; OMIA:001674-9615; nota: parte de la literatura usa crd4 para C2orf71/PCARE de Gordon/Irish setter (Downs LM et al. 2013. PMID: 22686255)
5. Enfermedad de Lafora: Lohi H et al. 2005. Expanded repeat in canine epilepsy. Science. PMID: 15637270; Barrientos L et al. 2019. NHLRC1 dodecamer repeat expansion in a Chihuahua with Lafora disease. Anim Genet. PMID: 30525203; von Klopmann T et al. 2021. Canine Lafora disease: an unstable repeat expansion disorder. Life (Basel). PMID: 34357061; OMIA:000690-9615