Cataracts (hereditary)

 

Gene: HSF4

Transmission: Autosomal recessive / Autosomal dominant

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.

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.

Mutations:

French Bulldog mutation (recessive): Insertion, HSF4 gene; c.971 ins.C, p.(L325T fs STOP 28), exon9

Australian Shepherd mutation (dominant): Deletion, HSF4 gene; c.971 del.C, p.(P324H fs STOP 87), exon9

Medical system: Ocular

Breeds: Australian Shepherd, Boston Terrier, Fox Terrier - Wire, French Bulldog, Miniature American Shepherd, Miniature Australian Shepherd, Staffordshire Bull Terrier, Toy Australian Shepherd

Age of onset of symptoms: For the recessive form (as seen with the Boston Terrier), cataracts are seen a few weeks to a few months after birth.  For the dominant form (as seen in Australian Shepherds) cataracts can occur throughout the lifetime of the dog.

Cataracts can be caused by the genetics of the animal, by the environment, or by a combination of the two.  Cataracts are opacities in the lens of the eye due to changes in the proteins of the lens. These opacities prevent the light from reaching the retina at the back of the eye, causing the dog’s vision to get washed out and blurry.  For the recessive form of hereditary cataracts, small cataracts appear a few weeks to a few months after the birth of the puppy.  These cataracts will evolve over time until the dog becomes completely blind around the age of 2 to 3 years. Hereditary cataracts are usually seen in both eyes.  It must be said that the genetics behind hereditary cataracts is complex, and while a couple of mutations are now described for several dog breeds there are still other mutations that await characterization.

 

References:

OMIA link: [1758-9615]

Genetics Committee of the American College of Veterinary Opthalmologists. (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]

Lewis TW, Mellersh, CS. (2019) Changes in mutation frequency of eight Mendelian inherited disorders in eight pedigree dog populations following introduction of a commercial DNA test. PLoS One 14:e0209864. [pubmed/30650096]

Ricketts SL, Pettitt L, McLaughlin B, Jenkins CA, Mellersh CS. (2015) A novel locus on canine chromosome 13 is associated with cataract in the Australian Shepherd breed of domestic dog. Mamm Genome 26(5-6) :257-263. [pubmed/25894238]

Mellersh CS, McLaughlin B, Ahonen S, et al. (2009) Mutation in HSF4 is associated with hereditary cataract in the Australian Shepherd. Veterinary Ophthalmology 12,6,372-378. [pubmed/19883468]

Mellersh CS, Graves KT, McLaughlin B, et al. (2007) Mutation in HSF4 associated with early but not late-onset hereditary cataract in the Boston Terrier. Journal of Heredity 98(5):531-533. [pubmed/17611257]

Mellersh CS, Pettitt L, Forman OP, et al. (2006) Identification of mutations in HSF4 in dogs of three different breeds with hereditary cataracts. Veterinary Ophthalmology 9,5,369-378. [pubmed/16939467]