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Polina Prokhoda, Erica Woertz, Erin Curran, Deborah Costakos, Joseph Carroll; The Effect of Tyrosinase Hypomorphic Alleles on Visual Acuity in Patients with Albinism. Invest. Ophthalmol. Vis. Sci. 2022;63(7):612 – A0327.
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© ARVO (1962-2015); The Authors (2016-present)
To examine the effect of hypomorphic alleles in the tyrosinase gene (TYR) on best corrected visual acuity (BCVA) in patients with albinism.
We retrospectively analyzed BCVA and genetic data from 75 individuals with suspected albinism. We did not include individuals with a history of premature birth or retinal pathology, or those who had mutations in multiple albinism genes. Patients were organized by albinism subtype and number of mutations. For individuals with OCA1, 16 had a single pathogenic TYR mutation, while 25 had two or more pathogenic TYR mutations. For individuals with OCA2, 10 had a single pathogenic mutation and 17 had two pathogenic mutations. Seven individuals had OA1 caused by hemizygous mutations in GPR143. For each albinism subtype, we further grouped individuals based on the number of TYR hypomorphic alleles that were identified. One-way ANOVA and Tukey’s multiple comparisons tests were performed to assess the difference in BCVA within groups.
For patients with OCA1 who had two or more pathogenic mutations, we observed a significant difference in BCVA between the TYR hypomorphic allele groups (p=0.0013). Post hoc testing revealed significant differences between patients with zero versus two hypomorphic alleles (p=0.04) and one versus two hypomorphic alleles (p=0.001). For subjects with OCA1 who had one pathogenic mutation, there was no significant difference in BCVA between the TYR hypomorphic allele groups (p=0.56). For subjects with OCA2 who had either one or two pathogenic mutations, there was no significant difference in BCVA between the TYR hypomorphic allele groups (p=0.96 and p=0.22, respectively). For subjects with OA1, there was no significant difference in BCVA between the TYR hypomorphic allele groups (p=0.67).
In patients with OCA1 with two or more pathogenic mutations, the presence of hypomorphic alleles in TYR is associated with worse visual acuity, which could be due to further reduced tyrosinase function. While TYR hypomorphic alleles have been shown to alter foveal structure in individuals with normal vision,1 it remains to be seen if the hypomorphic allele-related changes in visual acuity described here are also associated with changes in foveal structure in albinism.1: PMC8143408
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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