Oculocutaneous albinism in a patient with an OCA2 variant: molecular and clinical insights.

Background: Albinism is a rare genetic condition characterized by hypopigmentation of the skin, hair, and eyes, as well as visual impairments. Oculocutaneous albinism type 2 (OCA2) is commonly associated with variants in the OCA2 gene, which encodes a protein critical for melanosomal pH regulation and melanin biosynthesis. Exome sequencing, validated by Sanger sequencing, was employed to investigate the genetic basis of albinism in a consanguineous Iranian family. Bioinformatics analyses and structural modeling were conducted to assess the pathogenicity and impact of the detected variant.

Case presentation: A 27-year-old male from a consanguineous Iranian family presented with features of oculocutaneous albinism, including white hair, blue eyes, strabismus, sun-sensitive skin, reduced visual acuity, and significant photophobia, resulting in functional limitations in bright environments. Genetic analysis identified a novel homozygous missense variant in the OCA2 gene, NM_000275.3:c.1274T>G (p.Met425Arg), located in exon 13. The genomic coordinates of the variant are chr15:g.27985154A>C (GRCh38/hg38). In silico tools classified the variant as likely pathogenic based on its evolutionary conservation, absence in population databases, and structural modeling predictions. Segregation analysis confirmed autosomal recessive inheritance, with both parents being heterozygous carriers.

Conclusion: The identified OCA2 variant, c.1274T>G; p.Met425Arg, disrupts protein function, impairing melanosomal activity and melanin biosynthesis. This study underscores the importance of genetic analysis in characterizing OCA2 variants and highlights the need for further exploration of molecular mechanisms and phenotypic variability in OCA2-related albinism to improve diagnosis and counseling.