Genotype-Phenotype Correlation in a Cohort of Israeli Patients With OCA1 Albinism

The purpose of this study was to characterize genotype-phenotype associations in groups of patients with biallelic TYR gene pathogenic variants.

A retrospective study of patients with oculo-cutaneous albinism type 1 (OCA1) with identified biallelic TYR pathogenic variants followed between 2009 and 2025. The primary outcome was binocular best corrected visual acuity (BCVA). Secondary outcomes included refractive errors, strabismus, nystagmus, foveal hypoplasia, transillumination defects, fundus pigmentation, and photophobia.

Seventy-one patients with OCA1A and 223 with OCA1B were included. Eleven prevalent founder pathogenic variants account for almost 98% of unrelated TYR alleles in the Israeli Jewish population. The range of phenotypes for each genotype was determined. Patients with OCA1A had similar, significantly worse clinical outcomes compared to patients with OCA1B. Compound heterozygotes for an OCA1A allele and either c.1037-7T>A or the "Jewish-Yemenite haplotype" had worse BCVA and other ophthalmic measures compared to an OCA1A allele and either c.649C>T or the haplotype c.[575C>A;1205G>A], all causing OCA1B. Compound heterozygotes for c.1037-7T>A and an OCA1A allele also had significantly worse albinotic characteristics compared to c.1037-7T>A homozygotes or compound heterozygotes with either c.1217C>T or c.[575C>A;1205G>A].

Homozygotes or compound heterozygotes for pathogenic variants causing OCA1A all exhibited essentially the same phenotype. Contrary, patients having various OCA1B genotypes demonstrated significant differences in clinical features. This information can be used for prediction of expected phenotype, early diagnosis, and possibly improved clinical care, and hence it is of interest for parents of young patients and carrier couples. Additionally, genotype-phenotype correlations may improve the understanding of tyrosinase functions.