| 1. |
- Bergström, Tomas F.
(författare)
-
A novel mutation in TTC8 is associated with progressive retinal atrophy in the golden retriever
- 2014
-
Ingår i: Canine Genetics and Epidemiology. - : Springer Science and Business Media LLC. - 2052-6687. ; 1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Generalized progressive retinal atrophy (PRA) is a group of inherited eye diseases characterised by progressive retinal degeneration that ultimately leads to blindness in dogs. To date, more than 20 different mutations causing canine-PRA have been described and several breeds including the Golden Retriever are affected by more than one form of PRA. Genetically distinct forms of PRA may have different clinical characteristics such as rate of progression and age of onset. However, in many instances the phenotype of different forms of PRA cannot be distinguished at the basic clinical level achieved during routine ophthalmoscopic examination. Mutations in two distinct genes have been reported to cause PRA in Golden Retrievers (prcd-PRA and GR_PRA1), but for approximately 39% of cases in this breed the causal mutation remains unknown. Results: A genome-wide association study of 10 PRA cases and 16 controls identified an association on chromosome 8 not previously associated with PRA (praw = 1.30×10-6 and corrected with 100,000 permutations, pgenome = 0.148). Using haplotype analysis we defined a 737 kb critical region containing 6 genes. Two of the genes (TTC8 and SPATA7) have been associated with Retinitis Pigmentosa (RP) in humans. Using targeted next generation sequencing a single nucleotide deletion was identified in exon 8 of the TTC8 gene of affected Golden Retrievers. The frame shift mutation was predicted to cause a premature termination codon. In a larger cohort, this mutation, TTC8c.669delA, segregates correctly in 22 out of 29 cases tested (75.9%). Of the PRA controls none are homozygous for the mutation, only 3.5% carry the mutation and 96.5% are homozygous wildtype. Conclusions: Our results show that PRA is genetically heterogeneous in one of the world's numerically largest breeds, the Golden Retriever, and is caused by multiple, distinct mutations. Here we discuss the mutation that causes a form of PRA, that we have termed PRA2, that accounts for approximately 30% of PRA cases in the breed. The genetic explanation for approximately 9% of cases remains to be identified. PRA2 is a naturally occurring animal model for Retinitis Pigmentosa, and potentially Bardet-Biedl Syndrome.
|
|
| 2. |
|
|
| 3. |
- Bergström, Tomas F.
(författare)
-
Assessment of a Novel Pigmentary Chorioretinopathy in the Chinese Crested Dog
- 2014
-
Ingår i: JSM Ophthalmology. - 2333-6447. ; 2
-
Tidskriftsartikel (refereegranskat)abstract
- One hundred and twenty seven privately owned Chinese Crested Dogs (CCDs) were screened for Presumed Inherited Eye Disease (PIED). Thirty five cases of a recently discovered presumed inherited pigmentary chorioretinopathy were diagnosed and used for preliminary characterization of the disease using clinical and laboratory methods. Electroretinography (ERG) in ten affected and in nine normal CCDs was performed and morphology was obtained in one normal and in three affected 6-8 year-old dogs. A bilateral and mainly symmetrical retinal dystrophy with circumscribed pigmented lesions was observed, the earliest changes observed in 3-year-old dogs. The lesions showed a lighter center (pimple-like) and areas between lesions were often grayish and hypo reflective. Changes were mainly prevalent in the peripheral fundus initially. In more advanced cases the circumscribed pigmented changes were also observed centrally. In some cases there was diffuse hyper reflectivity in the area of the pigmented changes and slight vascular attenuation, indicating more generalized retinal degeneration. ERGs were not diagnostic in the early disease stage. Morphology showed changes at the level of the Retinal Pigment Epithelium (RPE), with focal areas of increased layering of RPE cells and detachment of RPE cells with subretinal migration. There were also areas of severe RPE and photoreceptor degeneration or atrophy with outer nuclear layer remnants in direct contact with the choroidal tissue. The circumscribed pigmented lesions observed ophthalmoscopically corresponded to these areas of geographic atrophy. The disease appears to be slowly progressive and in some cases, but not all, the disorder results in visual impairment or blindness.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Olsén, Lena, et al.
(författare)
-
Progressive retinal atrophy in the Polski Owczarek Nizinny dog: a clinical and genetic study
- 2016
-
Ingår i: Veterinary Ophthalmology. - : Wiley. - 1463-5216 .- 1463-5224. ; 19, s. 195-205
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To describe ophthalmic, functional, structural, and genetical characteristics of progressive retinal atrophy (PRA) in the polski owczarek nizinny (PON) breed of dog. Animals studied clinically Client-owned PON dogs (n = 82) from Sweden. Procedures Routine examination for presumed inherited eye disease was performed in all dogs. Bilateral full-field electroretinography (ERG) was performed in 11 affected and 4 control dogs. Eyes from one affected dog were studied with light microscopy. DNA samples from 34 Swedish and 30 PON dogs collected by Michigan State University (MSU) were tested for the mutations causing the rcd4 and prcd forms of PRA. Results Sixteen of the eighty-two Swedish dogs were diagnosed with PRA. Slight vascular attenuation, first seen at 4.5 years of age, preceded changes in tapetal reflectivity. The initial ERG changes in affected dogs showed markedly diminished rod responses, while cone responses were barely affected. Eventually, cone responses were also reduced. Retinal morphology showed approximately a 50% reduction of photoreceptor nuclei in the outer nuclear layer. Fourteen of fifteen PRA-affected Swedish dogs and eighteen of twenty of the MSU PRA-affected dogs tested genetically were positive for the rcd4 mutation. All tested dogs were negative for the mutation causing prcd-PRA. Conclusions PRA of PON dogs is a late-onset degenerative disease with slow progression. There is early loss of rod function, while the cone system deteriorates later. The rcd4 mutation in the C2ORF71 gene was associated with the majority of the PRA cases tested. The possibility of additional forms of PRA in the breed cannot be excluded.
|
|
| 10. |
|
|
