Whole-genome sequencing identifies missense mutation in GRM6 as the likely cause of congenital stationary night blindness in a Tennessee Walking Horse.

BACKGROUND: The only known genetic cause of congenital stationary night blindness (CSNB) in horses is a 1378 bp insertion in TRPM1. However, an affected Tennessee Walking Horse was found to have no copies of this variant. OBJECTIVES: To identify the genetic cause for CSNB in an affected Tennessee Walking Horse. STUDY DESIGN: Case report detailing a whole-genome sequencing (WGS) approach to identify a causal variant. METHODS: A complete ophthalmic exam, including an electroretinogram (ERG), was performed on suspected CSNB-affected horse. WGS data were generated from the case and compared with data from seven other breeds (n = 29). One hundred candidate genes were evaluated for coding variants homozygous in the case and absent in all other horses. Protein modelling was used to assess the functional effects of the identified variant. A random cohort of 90 unrelated Tennessee Walking Horses and 273 horses from additional breeds were screened to estimate allele frequency of the GRM6 variant. RESULTS: ERG results were consistent with CSNB. WGS analysis identified a missense mutation in metabotropic glutamate receptor 6 (GRM6) (c.533C>T p.Thr178Met). This single nucleotide polymorphism (SNP) is predicted to be deleterious and protein modelling supports impaired binding of the neurotransmitter glutamate. This variant was not detected in 273 horses from three additional breeds. The estimated allele frequency in Tennessee Walking Horses is 10%. MAIN LIMITATIONS: Limited phenotype information for controls and no additional cases with which to replicate this finding. CONCLUSIONS: We identified a likely causal recessive missense variant in GRM6. Based on protein modelling, this variant alters GRM6 binding, and thus signalling from the retinal rod cell to the ON-bipolar cell, impairing vision in low light conditions. Given the 10% population allele frequency, it is likely that additional affected horses exist in this breed and further work is needed to identify and examine these animals.

Corneal hypoesthesia, aqueous tear deficiency, and neurotrophic keratopathy following micropulse transscleral cyclophotocoagulation in dogs.

OBJECTIVE: To describe ocular surface complications following micropulse transscleral cyclophotocoagulation (MP-TSCPC) in dogs. ANIMALS STUDIED: Eighteen dogs treated with MP-TSCPC at two institutions for glaucoma management. PROCEDURES: MP-TSCPC was applied to each eye (avoiding 3 and 9 o'clock positions) with 31.3% duty cycle, 2000-3000 mW energy, and 90-180 seconds duration per hemisphere. Central corneal tactile sensation (CTS) and Schirmer tear test-1 (STT-1) were measured at baseline and ≥2 post-operative visits in each dog. RESULTS: Corneal sensitivity decreased in 16/18 dogs (89%) by an average of 10%-42% (up to 100% in 4 dogs). CTS decline was rapid (≤1 week) and only fully recovered in 50% of dogs within 8-180 days. Patients' age, glaucoma duration, laser energy, and total energy delivered did not affect CTS at any visit. However, brachycephalic dogs had significantly lower CTS and likelihood to recover full sensation compared with nonbrachycephalic dogs. Aqueous tear deficiency (STT-1 < 15 mm/min) occurred in 8/18 dogs (44%) within 7-270 days, and concurrent signs of keratoconjunctivitis sicca were noted in 2/18 dogs (11%). Neurotrophic corneal ulcers developed in 6/18 dogs (33.3%) and required 16-53 days to heal. CONCLUSIONS: Corneal hypoesthesia is a common complication of MP-TSCPC in dogs, and can lead to serious adverse effects such as aqueous tear deficiency and neurotrophic corneal ulcers. Brachycephalic dogs represent a population at higher risk. Close monitoring of ocular surface health is recommended for months following MP-TSCPC in dogs.