Macular Corneal Dystrophy

Gene: CHST6

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: Substitution, CHST6 gene, c.814 C>A, p.(R272S), chr.5.

Medical system: Ocular

Breeds: Labrador Retriever

Age of onset of symptoms: Between 4.5 and 6 years.

A phenotype of cloudy eyes and vision impairment was observed in a large but related pedigree of European Labrador Retrievers, and a diagnosis of macular corneal dystrophy (MCD) was made.  Ophthalmological observations revealed multiple, progressive corneal opacites in both eyes and accompanying corneal vascularization.  Histopathology revealed acidophilic granular material within the extracellular stroma of the cornea, consisting of keratin sulfate deposition and glycosaminoglycan accumulation.   Molecular studies identified a homozygote mutation in the CHST6 gene as the genetic cause of the MCD in the dog, as is the case in humans.   The CHST6 gene codes for a carbohydrate sulfotranserase enzyme that is specific to the cornea and that is important for maintaining keratin sulfate solubility in the corneal stroma.  Mutations in CHST6 cause keratin sulfate to precipitate, resulting in the corneal opacity observed in MCD.  A survey of 89 Labrador retrievers not related to the original study pedigree revealed a carrier frequency of 3.4% for the CHST6 mutation.  The availability of a DNA test will allow breeders to identify carrier animals and enable them, through selective breeding, to eliminate the disease and the mutation from their breed.

References:

OMIA link: [2071-9615]

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]

Busse C, Kafarnik C, Linn-Pearl R, Volmer C, et al. (2019) Phenotype of Macular Corneal Dystrophy in Labrador Retrievers: A Multicenter Study. Vet Ophthalmol. 22(3):294-304. [pubmed/30701649]

Tetas Pont R, Downs L, Pettitt L, Busse C, Mellersh CS. (2016) A Carbohydrate Sulfotransferase-6 (CHST6) Gene Mutation Is Associated With Macular Corneal Dystrophy in Labrador Retrievers.  Vet Ophthalmol. 19(6):488-492. [pubmed/26585178]

Contributed by:  Marilou Brisson and Victoria Leblanc, class of 2028, Veterinary Medicine Faculty, University of Montreal.  (Translation: DWS).