Stargardt disease

Stargardt disease is an inherited degenerative disease of the retina causing visual impairment and even total blindness. It is characterized by deposition of lipofuscin and vitamin A metabolites in the retinal pigment epithelium and weakening of the blood vessels that nourish the retina. This leads to progressive degeneration of rods and cones. The symptoms are particularly evident in older dogs, which have dilated pupils and abnormal reflex responses to glare. Daytime vision and dim light vision are significantly impaired.

The disease is caused by a loss-of-function mutation in the ABCA4 gene. It is a C insertion (c.4176insC) that leads to a reading frame shift and premature inclusion of a stop codon in exon 28 (p.F1393Lfs*1395). The ABCA4 gene encodes a membrane transporter protein localized in the outer segments of rod and cone photoreceptors; the mutation results in truncation of this protein and loss of function.

The genetic test can clearly reveal the genotype of the animal and is a useful tool for breeders to prevent unintentional breeding of affected puppies.

The disease affects dogs with P/P (positive / positive) genotype only. Dogs with P/N (positive /negative) genotype are clinically without any symptoms. They are genetically considered carriers of the disease (heterozygotes). In offspring of two heterozygous animals following genotype distribution can be expected: 25 % N/N (healthy non-carriers), 25 % P/P (affected), and 50 % N/P (healthy carriers). Because of high risk of producing affected offspring, mating of two N/P animals (carriers) can not be recommended.

.

Reference:

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. : An ABCA4 loss-of-function mutation causes a canine form of Stargardt disease. PLoS Genet 15:e1007873, 2019. Pubmed reference: 30889179. DOI: 10.1371/journal.pgen.1007873.