Leber congenital amaurosis

(Congenital night blindness)

 

Gene: RPE65

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Deletion, RPE65 gene; c.460_463 del. AAGA, p.(K154L fs STOP 53), exon5

Medical system: Ocular

Breeds: Beagle, Briard

Age of onset of symptoms: By 5 weeks, but variable.

Leber’s congenital amaurosis is a congenital retinal anomaly seen in the Briard.  It manifests itself in affected puppies through a defect in rod photoreceptor cells and a problem with night vision.  The disease progresses slowly, eventually also affecting the cone photoreceptor cells in the fundus of the retina.  By the age of 2 or 3, the affected dog will also have daytime vision problems.

 

References:

OMIA link: [1222-9615]

Genetics Committee of the American College of Veterinary Ophthalmologists. (2021) The Blue Book: Ocular disorders presumed to be inherited in purebred dogs. 13th Edition.  [https://ofa.org/wp-content/uploads/2022/10/ACVO-Blue-Book-2021.pdf]

Kondo M, Das G, Imai R, Santana E, et al. (2015)  A Naturally Occurring Canine Model of Autosomal Recessive Congenital Stationary Night Blindness.  PLoS One. 10(9):e0137072.  [pubmed/26368928]

Miyadera K, Acland GM, Aguirre GD. (2012) Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies. Mamm Genome 23:40-61.  [pubmed/22065099]

Hernández M, Pearce-Kelling SE, Rodriguez FD, et al. (2010) Altered expression of retinal molecular markers in the canine RPE65 model of Leber congenital amaurosis. Invest Ophthalmol Vis Sci. 51(12):6793-802. [pubmed/20671290]

Veske A, Nilsson SEG, Narfstrom K, Gal A. (1999) Retinal dystrophy of swedish Briard/Briard-Beagle dogs is due to a 4-bp deletion in RPE65. M Genomics 57:57-61. [pubmed/10191083]

Aguirre GD, Baldwin V, Pearce-Kelling S, et al. (1998) Congenital stationary night blindness in the dog: common mutation in the RPE65 gene indicates founder effect. Mol Vis. 4:23. [pubmed/9808841]

 

Contributed by: Sabrina Caroselli and Roxanne Richer, class of 2027, Veterinary Medicine Faculty, University of Montreal.  (Translation: DWS).