Ocular Phenotypes and Novel SLC45A2 Variants in Patients with Oculocutaneous Albinism Type 4

SLC45A2-related oculocutaneous albinism type 4 (OCA4) is a genetically defined subtype of albinism; however, its ocular phenotype remains incompletely characterized. This study aimed to describe the systemic, ophthalmic, and genetic features of patients with genetically confirmed SLC45A2-related OCA4.

Ninety patients with clinically diagnosed albinism were enrolled and underwent genetic testing. Patients with genetically confirmed SLC45A2-related OCA4 were included for further analysis. Demographic information, systemic pigmentation features, ophthalmic findings, and SLC45A2 variants were analyzed.

Five unrelated patients with genetically confirmed SLC45A2-related OCA4 were included, aged 5-33 years. Best-corrected visual acuity ranged from 0.1 to 1.0 logMAR, and spherical equivalent refractive error varied widely from -7.25 to +7.63 D. All patients exhibited iris transillumination defects and moderate-to-severe fundus hypopigmentation, both graded 2-3. Foveal hypoplasia was universally present, ranging from grade 1 to grade 4, with three patients showing grade 4 hypoplasia. Genetic analysis revealed nine disease-associated alleles representing eight distinct SLC45A2 variants: seven missense variants and one splice-altering variant. One patient carried a homozygous variant, and four carried compound heterozygous variants. Three novel variants were identified: c.1459C>G (p.Gln487Glu), c.137A>G (p.Glu46Gly), and c.561A>G.

This study characterizes the ocular phenotype of SLC45A2-related OCA4, including iris transillumination defects, fundus hypopigmentation, and foveal hypoplasia of varying severity. Three novel SLC45A2 variants were identified, expanding the mutational spectrum of OCA4.