Inherited Cataract HSF4-1 Test Code 207
For breeds: Staffordshire Bull Terriers, Boston Terriers and French Bulldogs
Inherited Cataract HSF4-2 Test Code 208
For breeds: Australian Shepherds (all varieties) & Miniature American Shepherds
OptiGen is pleased to offer the HSF4 tests through licensing by the Animal Health Trust where this cataract research was primarily conducted. Two mutations in the heat shock transcription factor gene, HSF4, have been reported to be associated with hereditary cataracts (HC) in several breeds of pure-bred dogs (1). One mutation (HSF4-1) observed in the Staffordshire Bull Terrier, Boston Terrier and French Bulldog acts as an autosomal recessive and results in the development of the juvenile form of cataract in dogs homozygous for the mutation. Cataracts caused by HSF4-1 are typically symmetrical in both eyes, first observed when pups are a few weeks to months of age and progressing to total lens cataract by 2-3 years of age. The heterozygous carriers of HSF4-1 are clinically unaffected.
A different mutation (HSF4-2) in the same gene is found in the Australian Shepherd. Unlike the HSF4-1 mutation, the Australian Shepherd mutation is inherited in an incomplete dominant manner, meaning that presence of just one copy of the mutation can lead to developing cataract (1). A study based on 392 Australian Shepherds indicates that about 50% of dogs carrying one copy of the deletion develop bilateral posterior cataracts when they are about 5 years old, while homozygotes (i.e. dogs carrying two copies of the HSF4-2 mutation) are more likely to develop a nuclear form of cataract that typically progresses to complete cataract (2).
The studies of hereditary cataracts indicate that in addition to HSF4 mutations there are other genetic factors that can contribute to the development of the disease in the above mentioned breeds. For example, Boston Terriers suffer from both juvenile and late-onset forms of HC, and it has been shown that the HSF4 mutation is responsible for the early-onset cataract only (3). Similarly, there were dogs in the Australian Shepherd cohort, which were normal for the HSF4 mutation but developed various types of cataracts, indicating that additional mutations are likely to contribute to the development of cataracts in this breed (2).
Prevalence of HSF4 mutations
The frequency of the HSF4-2 mutation in the Australian Shepherd was estimated to be 16.6% based on 392 dogs from 12 different countries (2). Statistics on several thousand dogs confirm that the frequency of the mutation is quite high in this breed, with approximately 23% of Aussies being carriers of the HSF4-2 mutation. The frequency of the HSF4-1 mutation seems to be lower, with about 8% of the French population of Staffordshire Bull Terriers tested as carriers (4).
Breedings strategies for reducing frequency of deleterious mutations causing cataracts in dogs
The high frequency of HSF4 mutations and their significant association with hereditary cataracts in the above mentioned breeds call for careful planning of breeding strategies. Since both types of HSF4 mutations have profound deleterious effects on vision when two copies of the mutation are present, it is recommended that at least one member of a breeding pair has been DNA tested as Normal/Clear of the mutation. The increased risk of developing cataracts when only one copy of the HSF4-2 mutation is present should also be considered when making breeding choices in the Australian Shepherd. It should be noted, however, that the high frequency of the HSF4-2 mutation in the breed warrants caution in the quickly/entirely eliminating carriers from the breeding population as this could have adverse effects on the breed as a whole.
- Mellersh et al., 2006, Veterinary Ophthalmology 9: 369-378
- Mellersh et al., 2009, Veterinary Ophthalmology 12: 372-378
- Mellersh et al., 2008, Journal of Heredity 98: 531-533