Microphthalmia, Congenital Eye Disease (Wheaton)

 

Gene: RBP4

Transmission: Autosomal recessive; maternal inheritance

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, RBP4 gene; c.282_284 del.GAA, p.(K31 del), exon 2

Medical system: Ocular

Breeds: Chihuahua, Russell Terrier, Soft-coated Wheaten Terrier

Age of onset of symptoms: at birth

Congenital microphthalmia is an eye disease reported in the Soft Coated Wheaton Terrier where affected puppies are born with small eyes (microphthalmia) as well as underdeveloped choroid and retina.  The genetics of this disease is particular in that requires maternal heredity, where both the puppy and the mother must be double mutant (homozygous M/M) for the anomaly to occur in the puppy.  The mutation is in a gene coding for a transport protein for retinol (vitamin A).  Absorption of vitamin A by the digestive system of the mother as well as placental transfer of vitamin A to the fetus are both reduced.  Vitamin A is needed by the fetus for normal development of eye structures.

 

References:
OMIA link: [2151-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

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]

Kaukonen M, Woods S, Ahonen S, et al. (2018) Maternal Inheritance of a Recessive RBP4 Defect in Canine Congenital Eye Disease. Cell Rep. 23(9):2643-2652. [pubmed/29847795]

Chou CM, Nelson C, Tarlé SA, et al. (2015) Biochemical Basis for Dominant Inheritance, Variable Penetrance, and Maternal Effects in RBP4 Congenital Eye Disease. Cell 161(3):634-646. [pubmed/25910211]

 

Contributed by: Antoine Cournyer, Class of 2020, Faaculty of Veterinary Medicine, University of Montreal.