Unusual Autosomal Dominant Inheritance of Oculocutaneous Albinism Type 4 (OCA-4): Clinical and Functional Features...

Oculocutaneous albinism (OCA) is a complex genetic disorder characterized by reduced or absent pigmentation in the skin, hair, and eyes. Among the eight known subtypes, OCA-4 is caused by a mutation in SLC45A2, which plays a crucial role in melanin biosynthesis. While autosomal recessive inheritance is the most common pattern for all OCA subtypes, autosomal dominant cases are extremely rare. We report three patients from a Chinese family exhibiting autosomal dominant OCA-4. Clinical assessments evaluated pigmentation and ocular features in affected family members. Next-generation sequencing was performed to identify pathogenic variants, and functional studies in MNT-1 cells were performed to explore the variant's biological effects. Patients exhibited mild hypopigmentation and foveal hypoplasia, consistent with the OCA-4 phenotype. Genetic analysis identified a heterozygous c.208T>C (p.Tyr70His) variant in SLC45A2, the same variant that has been previously reported in association with autosomal dominant OCA-4. Functional studies demonstrated that this variant caused protein retention in the endoplasmic reticulum, resulting in reduced melanin production. This family represents the first documented cases of autosomal dominant OCA-4 in the Chinese population and only the second reported worldwide. Our findings confirm that the p.Tyr70His variant causes autosomal dominant OCA-4. This study deepens our understanding of OCA-4's genetic mechanisms and increases the complexity of its inheritance patterns in genetic counseling.