Glaucoma, Primary Open Angle (POAG), ADAMTS10 related

 

Gene: ADAMTS10

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease. Both parents of an affected animal must be carriers of at least one copy of the mutation. Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutations:

Beagle mutation: Substitution, ADAMTS10 gene; c.1981 G>A, p.(G661R), exon17

Norwegian Elkhound mutation: Substitution, ADAMTS10 gene; C1159 G>A, p.(A387T)

Medical system: Ocular

Breeds: Beagle, Carlin Pinscher, Miniature Pinscher, Norwegian Elkhound, Siberian Laika

Age of onset of symptoms: Between 8 and 16 months

Primary Open Angle Glaucoma is a genetic disorder that results in increased pressure in one or both eyes. The higher the pressure, the higher risk of damage. Clinical signs are when the eyeball increases in size and becomes painful during which time, the dog shows signs of discomfort, such as excessive blinking, tears and redness. The eye may be swollen and have cataracts. If left untreated, this disease can cause dislocation of the lens of the eye, permanent damage to the optic nerve, and loss of vision.

 

References:

OMIA link: [1870-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Pytak RA, Pirie CG, Harman CD, et al. (2023) Iris angiography in ADAMTS10 mutant dogs with open-angle glaucoma (ADAMTS10-OAG). Vet Ophthalmol.  [pubmed/36855027]

Genetics Committee of the American College of Veterinary Opthalmologists. (2021) The Blue Book: Ocular disorders presumed to be inherited in purebred dogs. 13th Edition.  [https://ofa.org/wp-content/uploads/2022/10/ACVO-Blue-Book-2021.pdf]

Jeanes EC, Oliver JAC, Ricketts SL, Gould DJ, Mellersh CS. (2019) Glaucoma-causing ADAMTS17 mutations are also reproducibly associated with height in two domestic dog breeds: selection for short stature may have contributed to increased prevalence of glaucoma. Canine genetics and epidemiology 6(5). [pubmed/31131111]

Oliver JAC, Rustidge S, Pettitt L, et al. (2018) Evaluation of ADAMTS17 in Chinese Shar-Pei with primary open-angle glaucoma, primary lens luxation, or both.  Am J Vet Res 79(1):98-106. [pubmed/29287154]

Graham KL, McCowan C, White A. (2017) Genetic and biochemical biomarkers in canine glaucoma.  Veterinary Pathology 54(2):194-203. [pubmed/27681326]

Komáromy AM, Petersen-Jones SM. (2015) Genetics of Canine Primary Glaucomas. Vet Clin North Am Small Anim Pract 45:1159-82. [pubmed/26277300]

Oliver JA, Forman OP, Pettitt L. (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(10):e0140436. [pubmed/26474315]

Kuchtey J, Kunkel J, Esson D, et al. (2013) Screening ADAMTS10 in Dog Populations Supports Gly661Arg as the Glaucoma-Causing Variant in Beagles. Invest Ophthalmol Vis Sci. 54(3):1881-6. [pubmed/23422823]

Kuchtey J, Olson LM, Rinkoski T, et al. (2011) Mapping of the disease locus and identification of ADAMTS10 as a candidate gene in a canine model of Primary open angle glaucoma.  PLos Genetics 7(2):e1001306. [pubmed/21379321]