ClinVar

In 6 of 167 patients with age-related macular dystrophy (ARMD2; 153800), Allikmets et al. (1997) found a gly1961-to-glu (G1961E) alteration in the ABCR gene. The associated pathology ranged from a few tiny juxtafoveal drusen in 1 eye of a patient (age 74 years), to confluent drusen and drusenoid retinal pigment epithelium (RPE) detachments (age 78 years), to various forms of soft to calcified macular drusen and extensive geographic atrophy (more than 1 disc diameter) (ages 81 and 82 years, respectively).

In a study of 150 families with recessive Stargardt disease (STGD1; 248200), Lewis et al. (1999) found that the G1961E mutation was present in 16 of 173 chromosomes in which mutation was identified. G1961E in heterozygous state had previously been associated with age-related macular degeneration. In 150 families with STGD1, a high frequency of ARMD in first- and second-degree relatives was found, suggesting that heterozygosity enhances susceptibility to ARMD.

In a 14-year-old female with cone dystrophy (CORD3; 604116), Kitiratschky et al. (2008) identified compound heterozygosity for a 5882G-A transition in exon 42 of the ABCA4 gene, resulting in the G1961E substitution, and a splice site mutation (601691.0030). The patient, who had onset of disease at 6 years of age, had a red-green defect of color vision, normal glare sensitivity and night vision, RPE atrophy of the macula and peripheral retina, central scotoma, and a reduced cone but normal rod electroretinogram (ERG). Both mutations were also identified in her affected brother, and their unaffected parents were each heterozygous for 1 of the mutations, respectively.

Lek et al. (2016) questioned the pathogenicity of this variant because the ExAC database lists 4 homozygotes with the variant as well as a high allele frequency (0.015) of the variant in the South Asian population.