Stargardt disease is a degenerative eye disorder resulting from the progressive loss of the photoreceptor cells that are responsible for sensing light. Affected dogs show a decline in vision with age but appear to retain some vision throughout their life.
Phenotype: Stargardt disease is aninherited degenerative eye disease that affects the retina, the region of the eye that senses light. Affected dogs will have a progressive decline in vision.
Mode of Inheritance: Autosomal recessive
Alleles: N = Normal, S = Stargardt disease variant
Breeds appropriate for testing: Labrador Retriever
Explanation of Results:
Dogs with N/N genotype do not have the variant thought to cause Stargardt disease in Labrador Retrievers.
Dogs with N/S genotypes have one copy of the Stargardt variant but will not develop Stargardt disease. If two carriers with are mated, approximately 25% of the puppies are predicted to develop disease and 50% are predicted to be carriers.
Dogs with S/S genotypes are homozygous for the variant associated with Stargardt disease in Labrador Retrievers and are expected to develop disease.
Stargardt disease is an inherited degenerative eye disorder impacting the photoreceptor cells (cells of the eye that detect light) of the eyes, known as cones and rods. The cones are the cells that detect bright light and are important for color vision. Rods are the photoreceptor cells that detect light at night or in other low light conditions. Affected individuals show impaired vision in both daylight and dim light conditions, but partial vision is retained throughout their lifetime. Clinical features of Stargardt disease include diffuse retinal degeneration and reduction of the number of photoreceptors, with profoundly abnormal cone cell function but rod cell function is impacted to a lesser extent.
A single nucleotide insertion in the ATP binding cassette subfamily A member 4 (ABCA4) gene of a cytosine (C) in exon 28 is associated with Stargardt disease in the Labrador retriever. This insertion (c.4176insC) affects the reading frame of the protein and leads to a premature stop codon at amino acid position 1395 (p.F1393Lfs*1395). The resulting protein is truncated, missing the last 874 amino acid residues compared to the normal ABCA4 protein. This shortened protein is thought to lead to toxic byproducts in the cell that result in photoreceptor degeneration. The mode of inheritance is autosomal recessive, which means that males and females are equally affected and that two copies of the variant are needed to cause Stargardt disease. Mutations in this same gene cause several clinically distinct ocular diseases including one with a similar presentation to this Labrador specific disease.
The Stargardt disease variant was first identified in a pair of Labrador retriever siblings (one male, one female). Additional testing confirmed the association of the variant with disease. Eye exams of 22 additional Labrador Retrievers identified eight clinically affected dogs. All were were homozygous for the c.4176insC variant, whereas fourteen showed no signs of retinal degeneration by seven years of age; seven of these were carriers and the remaining seven were homozygous for the normal allele.
The VGL offers a DNA test for Stargardt disease. Test results assist veterinarians with diagnosis of Stargardt disease and helps breeders identify carriers among breeding stock to select appropriate mates thus reducing the risk of producing affected offspring.
Normal. No copies of the Labrador Retriever Stargardt disease variant detected.
Carrier. One copy of the Labrador Retriever Stargardt disease variant detected.
Affected. Two copies of the Labrador Retriever Stargardt disease variant detected. The dog will likely have progressive vision decline.
Mäkeläinen, S., Gòdia, M., Hellsand, M., Viluma, A., Hahn, D., Makdoumi, K., Zeiss, C.J., Mellersh, C., Ricketts, S.L., Narfström, K., Hallböök, F., Ekesten, B., Andersson, G., & Bergström, T.F. (2019). An ABCA4 loss-of-function mutation causes a canine form of Stargardt disease. PLoS Genetics, 15(3), e1007873. doi: 10.1371/journal.pgen.1007873