Test Detail

Multi-disease genetic panel for the Golden retriever grouping six molecular tests: three forms of progressive retinal atrophy (prcd-PRA, GR-PRA1 and GR-PRA2), Golden retriever muscular dystrophy (MD/GRMD, homologous to Duchenne muscular dystrophy), congenital ichthyosis (forms ICH1 and ICH2, included in a single test) and neuronal ceroid lipofuscinosis type 5 (NCL5). Each condition has its own molecular basis, inheritance and prognosis. The panel is complementary to, not a substitute for, ophthalmological, neuromuscular and dermatological examination in breeding selection.

Applicable breed: Golden retriever. GR-PRA1: in the original study the variant was detected in ~56% of the PRA cases analysed and in ~87% of obligate carriers, with approximate frequencies of 4% (United Kingdom), 6% (Sweden) and 2% (France), and not detected in the USA (Downs 2011). prcd-PRA and GR-PRA2 are present in breeding lines; ichthyosis ICH1 is relatively frequent and ICH2 appears rare and restricted to North American lines; GRMD and NCL5 have low case numbers. There are no reliable carrier frequencies in the breeding population (limited data).

- Initial night blindness and progressive retinal atrophy, evolving to blindness (prcd-PRA, GR-PRA1, GR-PRA2)
- Fundus with tapetal hyperreflectivity and vascular attenuation (PRA)
- Progressive muscle weakness from puppyhood, with initial hypertrophy and progressive atrophy; bunny-hopping gait and difficulty rising (MD/GRMD)
- Dyspnoea due to weakness of the intercostal muscles and cardiac involvement (MD/GRMD)
- Generalized scaling from the first weeks, non-inflammatory; greasy or unkempt coat (ichthyosis ICH1/ICH2)
- Behavioural changes, ataxia, myoclonus or seizures, visual deterioration and cachexia (NCL5)

prcd-PRA was associated with the PRCD gene and its test became widespread across multiple breeds (Zangerl 2006; Goldstein 2006). PRA in the Golden is genetically heterogeneous: Downs et al. (2011) identified GR-PRA1 in SLC4A3 and Downs et al. (2014) GR-PRA2 in TTC8. Golden retriever muscular dystrophy (GRMD) is the classic canine model of human Duchenne muscular dystrophy and is due to a processing error of dystrophin mRNA (DMD, X-linked) described by Sharp et al. (1992). Congenital ichthyosis was associated with PNPLA1 (ICH1; Grall 2012) and, in North American lines, with ABHD5 (ICH2; Kiener 2022). NCL in the Golden is due to a variant specific to CLN5 (Gilliam 2015), distinct from that of the Border collie and Australian cattle dog.

- Genotype breeding animals with the combined panel before mating (PRA is heterogeneous: a negative result for one variant does not rule out another)
- prcd-PRA, GR-PRA1, GR-PRA2, ichthyosis (ICH1/ICH2) and NCL5 (recessive): do not mate two carriers (25% affected homozygotes); carrier x clear is acceptable if the offspring intended for breeding is tested
- MD/GRMD (X-linked): do not breed affected males; carrier females only with non-carrier males; daughters of an affected father are obligate carriers
- In a puppy with scaling from suckling, request the combined PNPLA1+ABHD5 test before any mating of the parents
- After a confirmed clinical case, do not repeat the parental mating and communicate the status to the buyer

The three PRAs are distinguished by age of onset and fundus appearance, but molecular diagnosis is what confirms the suspicion; annual eye examination (ECVO/CERF) and electroretinography when appropriate. GRMD is confirmed by molecular study and by dystrophin immunohistochemistry on muscle biopsy; the differential diagnosis includes other congenital myopathies and myasthenia. Ichthyosis is confirmed by molecular test and biopsy; the differential includes dermatophytosis, demodicosis and primary seborrhoea. NCL5 requires molecular and histopathological confirmation; the differential includes other NCLs, idiopathic epilepsy and inflammatory encephalopathies.

1. prcd-PRA: Zangerl B et al. 2006. Identical mutation in a novel retinal gene causes progressive rod-cone degeneration in dogs. Genomics. PMID: 16938425; Goldstein O et al. 2006. Linkage disequilibrium mapping in domestic dog breeds narrows the progressive rod-cone degeneration interval. Genomics. PMID: 16859891
2. GR-PRA1 (SLC4A3): Downs LM et al. 2011. A frameshift mutation in golden retriever dogs with progressive retinal atrophy endorses SLC4A3 as a candidate gene. PLoS One. PMID: 21738669; OMIA:001572-9615
3. GR-PRA2 (TTC8): Downs LM et al. 2014. A novel mutation in TTC8 is associated with progressive retinal atrophy in the golden retriever. Canine Genet Epidemiol. PMID: 26401321; Mäkeläinen S et al. 2020. Deletion in the Bardet-Biedl syndrome gene TTC8 results in a syndromic retinal degeneration. Genes (Basel). PMID: 32962042; OMIA:001984-9615
4. MD/GRMD (DMD): Sharp NJ et al. 1992. An error in dystrophin mRNA processing in golden retriever muscular dystrophy. Genomics. PMID: 1577476; Kornegay JN. 2017. The golden retriever model of Duchenne muscular dystrophy. Skelet Muscle. PMID: 28526070
5. Ictiosis congénita (PNPLA1/ABHD5): Grall A et al. 2012. PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans. Nat Genet. PMID: 22246504; Kiener S et al. 2022. ABHD5 frameshift deletion in Golden Retrievers with ichthyosis. G3 (Bethesda). PMID: 34791225; OMIA:001588-9615 (PNPLA1; OMIA no recoge una entrada para ABHD5/ICH2)
6. NCL5 (CLN5): Gilliam D et al. 2015. Golden Retriever dogs with neuronal ceroid lipofuscinosis have a two-base-pair deletion and frameshift in CLN5. Mol Genet Metab. PMID: 25934231; Melville SA et al. 2005. A mutation in canine CLN5 causes neuronal ceroid lipofuscinosis in Border collie dogs. Genomics. PMID: 16033706; Kolicheski A et al. 2016. Australian Cattle Dogs with neuronal ceroid lipofuscinosis are homozygous for a CLN5 nonsense mutation. J Vet Intern Med. PMID: 27203721; OMIA:001482-9615