Congenital eye malformation (Golden Retriever)

Gene: SIX6

Transmission: Autosomal dominant, variable penetration

For an autosomal dominant genetic disease, an animal must have at least one copy of the mutation in question to be at risk of developing the disease.  Animals with two copies of the mutation generally have more severe symptoms and an earlier onset of the disease than animals with just one copy of the mutation.  One or both of the parents of an animal with the mutation has one or two copies of the mutation.  Animals that have one or two copies of the mutation can pass the mutation on to future generations.

Mutation: Substitution, SIX6 gene; c.719 G>A, p.(Arg240His), exon 4, chromosome 9

Medical system: Ocular

Breeds: Golden Retriever

Age of onset of symptoms: From birth.

The SIX6 gene codes for a homeobox transcription factor, known from human and mouse studies to be important for embryonic eye development.  Mutations of the SIX6 gene result in congenital eye anomalies.

In an extended pedigree with a common sire, Golden Retriever puppies were born with a variety of eye structural and functional defects of varying severity, including unilateral or bilateral retinal dysplasia, retinal detachement, optic nerve absence or hypoplasia, congenital cataracts and nystagmus.  Affected puppies displayed ataxia and bumped into objects.  Molecular studies revealed a null mutation within the SIX6 gene as the likely causative mutation, displaying autosomal dominant heredity with variable penetration.  The mutation was not found in 464 non related Golden Retriever samples suggesting that it was restricted to the pedigree in question and not of general concern for the breed.

References:

OMIA link: [2208-9615]

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]

Hug P, Anderegg L, Dürig N, et al. (2019) A SIX6 nonsense variant in Golden Retrievers with congenital eye malformations. Genes (Basel) 10(6):454.  [pubmed/31207931]

Contributed by: Anne-Sophie Perrault et Maria Enachescu, class of 2027, Veterinary Medicine Faculty, University of Montreal.  (Translation: DWS).