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Primary open angle glaucoma (ADAMTS17 gene, Basset Hound)

Primary open angle glaucoma (ADAMTS17 gene, Basset Hound)

Glaucoma is a heterogeneous inherited disorder characterized by an abnormal increase in intraocular pressure, which can lead to pain and even blindness. This disorder has been associated with mutations in specific genes, such as ADAMTS10 and ADAMTS17.

Symptoms

Primary open-angle glaucoma develops slowly over weeks to months. Symptoms include loss of vision, pain, appearance of vessels in the eye, redness, corneal clouding, tearing, pupils of different size, vision problems, eye swelling, lack of appetite and depression. Glaucoma is a medical emergency and requires immediate attention to avoid irreversible damage to the retina and optic nerve.

Disease Management

Treatment of open-angle glaucoma focuses on restoring normal eye pressure and reducing pain. Open-angle glaucoma comes on slowly and, at least initially, can be kept under control with medications. Topical and oral medications may be used to lower eye pressure and treat inflammation or infection. In more severe cases, different surgical options such as cyclophotocoagulation, gonioimplantation or enucleation may be used.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

Primary open-angle glaucoma is characterized by increased intraocular pressure due to an imbalance between the production and drainage of intraocular fluid (aqueous humor). Glaucoma is one of the leading causes of blindness worldwide. The ADAMTS17 gene belongs to the family of genes involved in the formation of elastic microfibril structures. This gene is expressed within the ciliary body, which is responsible for the production of aqueous humor and contributes to intraocular pressure. Furthermore, in the study by Hubmacher et al. (2017), the possibility was raised that the ADAMTS17 gene plays a role in the proper development of the ciliary zonule. This structure, being connected to the ciliary body, could contribute to the proper balance of aqueous humor. A deletion in exon 2 of the ADAMTS17 gene, which introduces a premature stop codon, has been identified in the Basset Hound breed. This deletion is expected to result in an 86.1% truncated protein, including the catalytic domain. As a result, a complete functional loss of the protein is generated.

Most affected breeds

Basset Hound

Bibliography

Hubmacher D, Schneider M, Berardinelli SJ, et al. Unusual life cycle and impact on microfibrillary assembly of ADAMTS17, a secreted metalloprotease mutated in genetic eye disease. Sci Rep. 2017 Feb 8;7:41871.

Oliver JA, Forman OP, Pettitt L, et al. 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. 2015 Oct 16;10(10):e0140436.