PCYT2 deficiency in Saarlooswolfdogs with progressive retinal, central, and peripheral neurodegeneration.

We investigated a syndromic disease comprising blindness and neurodegeneration in 11 Saarlooswolfdogs. Clinical signs involved early adult onset retinal degeneration and adult-onset neurological deficits including gait abnormalities, hind limb weakness, tremors, ataxia, cognitive decline and behavioral changes such as aggression towards the owner. Histopathology in one affected dog demonstrated cataract, retinal degeneration, central and peripheral axonal degeneration, and severe astroglial hypertrophy and hyperplasia in the central nervous system. Pedigrees indicated autosomal recessive inheritance. We mapped the suspected genetic defect to a 15 Mb critical interval by combined linkage and autozygosity analysis. Whole genome sequencing revealed a private homozygous missense variant, PCYT2:c.4A>G, predicted to change the second amino acid of the encoded ethanolamine-phosphate cytidylyltransferase 2, XP_038402224.1:(p.Ile2Val). Genotyping of additional Saarlooswolfdogs confirmed the homozygous genotype in all eleven affected dogs and demonstrated an allele frequency of 9.9% in the population. This experiment also identified three additional homozygous mutant young dogs without overt clinical signs. Subsequent examination of one of these dogs revealed early-stage progressive retinal atrophy (PRA) and expansion of subarachnoid CSF spaces in MRI. Dogs homozygous for the pathogenic variant showed ether lipid accumulation, confirming a functional PCYT2 deficiency. The clinical and metabolic phenotype in affected dogs shows some parallels with human patients, in whom PCYT2 variants lead to a rare form of spastic paraplegia or axonal motor and sensory polyneuropathy. Our results demonstrate that PCYT2:c.4A>G in dogs cause PCYT2 deficiency. This canine model with histopathologically documented retinal, central, and peripheral neurodegeneration further deepens the knowledge of PCYT2 deficiency.

Eyelid and conjunctival mast cell tumors: A retrospective study of 26 dogs and 8 cats.

OBJECTIVE: The objective of the study was to describe clinical and histologic characteristics of eyelid (LMCT) and conjunctival (CMCT) mast cell tumors in dogs and cats presented to a referral clinic in Germany. ANIMAL STUDIED: Medical records were reviewed to identify dogs and cats diagnosed with LMCTs or CMCTs between 2006 and 2020. RESULTS: LMCT were diagnosed in 31 patients and were cutaneous (n = 28; 20 dogs and 8 cats) or subcutaneous (three dogs). Five cases involved the mucocutaneous junction (four dogs, one cat). CMCTs occurred only in dogs (n = 3). At the time of presentation two of the four canine LMCT cases involving the mucocutaneous junction had metastasized to a mandibular lymph node. When applying the Kiupel system, both these cases were categorized as high grade. 85.7% (18/21) of the canine (19 cutaneous and 2 subcutaneous) LMCT and all CMCT cases were categorized as Kiupel low grade. No local recurrences occurred in all LMCT cases in which clean surgical margins were obtained (n = 18, mean surgical margin width: dogs 9.4 mm, cats 3.8 mm). Two cats (2/4) and four dogs (4/7) with questionable or incomplete surgical margins experienced local recurrences (mean time to recurrence of 180 and 637 days in dogs and cats, respectively). CONCLUSION: Recurrence of low-grade LMCTs and CMCTs following excision with clean margins is rare. Tumors involving the mucocutaneous junction may be of higher grade and prone to lymphatic metastasis.

Outcome of phacoemulsification following corneal and lens laceration in cats and dogs (2000-2010).

OBJECTIVE: To investigate the success rate of phacoemulsification following corneal and lens laceration in dogs and cats. PROCEDURE: Retrospective review of cats and dogs presenting with corneal and lens laceration and treated with phacoemulsification. RESULTS: The records of 33 patients (33 eyes: six feline, 27 canine) presenting to a private referral center were reviewed. Affected dogs were younger (median 18 months) than affected cats (median 30 months). The lacerations were caused by cat scratch trauma (9/33), thorn injury (6/33), and glass shards (1/33); the cause was unknown in 17/33 cases. All cats and 85.2% of all dogs were visual at the last examination. The median follow-up was 4 and 8 months for cats and dogs, respectively. In all canine cases that developed vision loss, this occurred within the first 14 weeks postoperatively. The ultimate cause for vision loss in dogs was secondary glaucoma (4/4) and retinal detachment (1/4). CONCLUSION: Cats have an excellent outcome and dogs a very good outcome following surgery for corneal and lens laceration. The cause of the trauma, the size of the lesion, the time interval between the ocular trauma and surgery, and the type of surgery were not found to have an influence on the outcome of patients in this study. We postulate that vision loss might develop more often in cases with complications associated with the initial corneal laceration wound.

Cataracts are not associated with retinal detachment in the Bichon Frise in the UK--a retrospective study of preoperative findings and outcomes in 40 eyes.

OBJECTIVE: The aim of this study was to evaluate whether the Bichon Frise population in the UK is at the same risk of developing retinal detachment in association with cataract formation and following phacoemulsification as described in reports from the USA. PROCEDURES: The medical records of Bichon Frises which were presented for cataract assessment and of those which were treated with phacoemulsification at Willows Referral Service between 1997 and 2009 were reviewed. RESULTS: Forty eyes (26 dogs) with unilateral or bilateral cataracts were included in the study. There was no evidence of retinal detachment associated with the cataracts at initial presentation. Phacoemulsification was performed on 34 eyes (20 dogs). Clinically evident lens-induced uveitis was treated preoperatively in 17/34 eyes. Artificial lens implantation was carried out in 30/34 eyes; automated anterior vitrectomy was performed in 7/34 eyes. The mean follow-up time was 16.6 months (range 1.5-73 months). At the last re-examination, 31/34 eyes (91.2%) were visual. Three eyes (8.8%) were blind--two (in the same dog) because of presumptive bilateral optic nerve disease and one because of uveitis and secondary glaucoma. There was no evidence of retinal detachment following phacoemulsification in any of the 34 eyes. CONCLUSION: This study suggests that the Bichon Frise population in the UK does not appear to have a predisposition for retinal detachment in association with cataract formation or following cataract surgery. Prophylactic random transscleral laser retinopexy or transscleral cryopexy cannot therefore be routinely recommended for Bichon Frises with cataracts in the UK.

Neuron-specific enolase antibodies in patients with sudden acquired retinal degeneration syndrome.

Sudden acquired retinal degeneration syndrome (SARDS) is a disease characterised by sudden and bilateral vision loss of dogs. Previous studies failed to identify the underlying cause [Mattson, A., Roberts, S.M., Isherwood, J.M.E., 1992. Clinical features suggesting hyperadrenocorticism associated with sudden acquired retinal degeneration syndrome in a dog. J. Am. Anim. Hosp. Assoc. 28, 199-202; Van der Woerdt, A., Nasisse, M.P., Davidson, M.G., 1991. Sudden acquired retinal degeneration in the dog: clinical and laboratory findings in 36 cases. Prog. Vet. Comp. Ophthamol. 1, 11-18] and earlier investigations about the occurrence of anti-retinal antibodies in SARDS patients showed inconsistent results. To provide a novel approach to those findings we designed a more detailed study. Autoantibodies of SARDS patients and normal controls were tested against the purified autoantigens S-antigen and cellular retinaldehyde binding protein (CRALBP) that play a role in human autoimmune uveitis. Next we tested the autoantibody binding pattern to whole retinal lysate. No difference in the incidence of autoantibodies could be found between SARDS patients and healthy controls while testing the well-known autoantigens S-antigen and CRALBP. Potential novel, yet unknown autoantigens were identified by a screening test using the retinal proteome as an autoantigenic source. In SARDS patients and normal controls, several retinal proteins were bound by IgG antibodies, but one band was strongly marked by SARDS patients. That band was excised, subjected to mass spectrometry (matrix-assisted laser desorption/ionisation-time of flight (MALDI-TOF/TOF)) and identified as neuron-specific enolase. Binding of the IgG autoantibodies of SARDS-affected dogs to this protein was verified using purified NSE, revealing 25% of NSE autoantibody-positive SARDS patients and 0% of negative controls. Our findings indicate that at least some dogs with SARDS have autoantibodies against NSE, although it is unclear whether these play a causative role in SARDS or whether they are the result of retinal destruction by another mechanism.