2.1 Cone-rod dystrophy
More than 40 mutations in the ABCA4 gene have been found to cause a vision disorder called cone-rod dystrophy. The problems associated with this condition include a loss of visual sharpness (acuity), an increased sensitivity to light (photophobia), and impaired color vision. These vision problems worsen over time. It is estimated that ABCA4 gene mutations account for 30 to 60 percent of cases of cone-rod dystrophy that are inherited in an autosomal recessive pattern, which means that both copies of the gene in each cell have mutations.
Most of the ABCA4 gene mutations that cause cone-rod dystrophy change single protein building blocks (amino acids) in the ABCA4 protein. The altered protein cannot remove N-retinylidene-PE from photoreceptor cells. As a result, N-retinylidene-PE combines with another substance to produce a molecule called N-retinylidene-N-retinylethanolamine (A2E), which builds up in these cells. The buildup of A2E is toxic to photoreceptor cells and leads to their deterioration, causing progressive vision loss in people with cone-rod dystrophy. Cone-rod dystrophy caused by ABCA4 gene mutations tends to be associated with more severe vision problems than cone-rod dystrophy caused by other genetic mutations.