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Keiko Miyadera, Gustavo D Aguirre; A new canine model of juvenile retinal degeneration: initial phenotypic characterization and implication of within-breed genetic heterogeneity. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4478.
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With over 25 distinct forms of naturally-occurring inherited retinal degenerations molecularly characterized to date, the domestic dog has provided excellent models for homologous human conditions including RP, LCA, achromatopsia and others. A late onset retinal degeneration (prcd) caused by a PRCD mutation has been known in the Portuguese Water Dog breed. Recently, we have identified a new form of retinal degeneration in the breed showing a significantly earlier, juvenile onset. Our aim was to characterize the clinical phenotype and to determine the mode of inheritance. Mutations associated with retinal degeneration in other canine breeds were screened to evaluate possible gene flow.
Ophthalmic examination was performed in the male proband, its sire, dam, and 5 full-siblings, and 7 other related dogs; examination included indirect ophthalmosocopy with fundus photography in selected cases. Additionally, 34 distantly related dogs were examined to ascertain phenotype. Pedigree was reconstructed to examine the mode of inheritance. Blood samples were obtained for DNA extraction and screening of known mutations.
Two full-sib females were found with phenotypic changes comparable to the proband. The onset of visual deficit in the affected cases was at 2-3 years of age at which time typical ophthalmoscopic changes of mid-stage disease were present: tapetal hypereflectivity, narrow retinal vessels, and pale optic disk. These gradually progressed with time. Pedigree analysis strongly indicated an autosomal recessive etiology. None of the known mutations screened were present in the cases, including the PRCD mutation.
We report a new model of juvenile-onset retinal degeneration in a highly inbred canine population in which a non-allelic late-onset retinal degeneration (prcd) also segregates. Given the more severe clinical nature of the newly identified retinal degeneration, a relatively recent popular sire effect and/or a consequence of breeding away from the known prcd allele, are indicated. Identification of additional cases affected with the juvenile form will facilitate mapping of the disease locus and identification of the underlying gene/mutation. Our goal is to elucidate the disease mechanism functionally, and explore therapeutic options in this valuable new canine model.
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