Furthermore, modifiers might also aggravate the ABCA4-AR phenotype of individuals; Leber's congenital amaurosis, causing severe vision loss in the first year of life, is usually not associated with variants in ABCA4, but Panneman et al. identified probands in which two ABCA4 null alleles are hypothesized to cause Leber's congenital amaurosis [49] (Panneman, Koenekoop, Cremers, unpublished data). This evidence concerns the gene AR and Leber congenital amaurosis.