Test Detail
Primary open-angle glaucoma (POAG) in scent hound-type breeds
Ocular · Dog
Hereditary open-angle glaucoma that appears in several scent hound-type breeds, with progressive increase in intraocular pressure, optic nerve damage and blindness. The molecular basis is heterogeneous: in some breeds it is due to mutations in ADAMTS17 and in others in ADAMTS10, two genes of the same family involved in the extracellular matrix of the iridocorneal angle and the zonules. It is inherited in an autosomal recessive manner.
Incidence
Affected breeds: Basset Hound (allelic frequency of the mutation ≈8% in the United Kingdom, n=223), Basset Fauve de Bretagne, Beagle, Norwegian Elkhound (25.3% carriers) and Griffon Vendéen (Petit Basset Griffon Vendéen, with a high incidence of POAG). The 4.96-Mb inversion variant is published only in the Petit Basset Griffon Vendéen; there is no published evidence that it applies to the Grand Basset Griffon Vendéen, so the test should not be extrapolated without verification.
Breeder management
- Test breeding animals with the breed-specific test (ADAMTS17 or ADAMTS10 as appropriate)
- Do not mate two carriers: 25% risk of affected homozygotes
- A carrier can be mated to a clear animal; offspring intended for breeding must be tested
- In the Norwegian Elkhound, given the high carrier frequency, prioritize systematic screening before breeding
- Exclude affected animals from breeding; also monitor stature, since an association with shorter height has been described in ADAMTS17 breeds
- Do not mate two carriers: 25% risk of affected homozygotes
- A carrier can be mated to a clear animal; offspring intended for breeding must be tested
- In the Norwegian Elkhound, given the high carrier frequency, prioritize systematic screening before breeding
- Exclude affected animals from breeding; also monitor stature, since an association with shorter height has been described in ADAMTS17 breeds
Specialist notes
Differential diagnosis with secondary glaucoma (uveitis, lens luxation, intraocular tumor) and with primary closed-angle glaucoma. Gonioscopy provides information about the angle, but confirmation is genetic. The molecular heterogeneity between ADAMTS10 and ADAMTS17 makes it necessary to use the correct variant for each breed; a negative result for one variant does not rule out POAG due to the other gene family. In ADAMTS17 breeds, lens luxation should also be monitored.
References
1. Oliver JAC, Forman OP, Pettitt L, Mellersh CS. (2015) Two independent mutations in ADAMTS17 are associated with primary open angle glaucoma in the Basset Hound and Basset Fauve de Bretagne breeds of dog. PLoS One 10:e0140436. PMID: 26474315
2. Forman OP, Pettitt L, Komáromy AM, Bedford P, Mellersh C. (2015) A novel genome-wide association study approach using genotyping by exome sequencing leads to the identification of a primary open angle glaucoma associated inversion disrupting ADAMTS17. PLoS One 10:e0143546. PMID: 26683476
3. Ahonen SJ, Kaukonen M, Nussdorfer FD, Harman CD, Komáromy AM, Lohi H. (2014) A novel missense mutation in ADAMTS10 in Norwegian Elkhound primary glaucoma. PLoS One 9:e111941. PMID: 25372548
2. Forman OP, Pettitt L, Komáromy AM, Bedford P, Mellersh C. (2015) A novel genome-wide association study approach using genotyping by exome sequencing leads to the identification of a primary open angle glaucoma associated inversion disrupting ADAMTS17. PLoS One 10:e0143546. PMID: 26683476
3. Ahonen SJ, Kaukonen M, Nussdorfer FD, Harman CD, Komáromy AM, Lohi H. (2014) A novel missense mutation in ADAMTS10 in Norwegian Elkhound primary glaucoma. PLoS One 9:e111941. PMID: 25372548