Glaucoma, Primary Open Angle, ADAMTS17 related

 

Gene: ADAMTS17

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:

Basset Hound mutation: Substitution, ADAMTS17 gene; c.194_213 del., p.(L68G fs STOP)

Basset Fauve de Bretagne mutation: Substitution, ADAMTS17 gene; c.1552 G>A, p.(G518S)

Petit Basset Griffon Vendéen mutation: Inversion, ADAMTS17 gene; 4.46 Mb intron 12.

Chinese Shar-Pei mutation: Deletion, ADAMTS17 gene; c.3069_3074 del, p.(V1024_V1025 del)

Medical system: Ocular

Breeds: American Staffordshire Terrier/Amstaff, Basset Fauve de Bretagne, Basset Hound, Petit Basset Griffon Vendeen, Pug, Shar Pei, Shih Tzu

Age of onset of symptoms: 3  to 4 years

Glaucoma is an eye disease characterized by increased fluid pressure within the eye caused by a blockage in the normal flow of aqueous humour. Primary glaucoma is normally caused by a genetic mutation that leads to a structural anomaly within the eye. Several natural mutations within the ADAMTS17 gene are the cause of hereditary glaucoma in a number of dog breeds.  The first clinical signs, observed by an ophthalmologist when the dog is 3 to 4 years of age, involve a slight increase in the pressure of the aqueous humour. The progression of the disease is slow, with gradual loss of peripheral vision. Eventually, intraocular pressure is increased, the eye is noticeably lager in size, and there is a degeneration of the retina that leads to blindness. Pain is not associated with these developments.

 

References:

OMIA link: [1976-9615]

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]

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]

Komáromy AM, Petersen-Jones SM. (2015) Genetics of Canine Primary Glaucomas. Vet Clin North Am Small Anim Pract. Nov;45(6):1159-82 [pubmed/26277300]

Forman OP, Pettitt L, Komáromy AM, et al. (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(12) :e0143546. [pubmed/26683476]

 

Contributed by: Antoine Cournyer, Class of 2020, Faculty of Veterinary Medicine, University of Montreal.