Molecular Characterization of a Recurrent Pathogenic TYR Variant in a Consanguineous Family with Oculocutaneous Albinism Type 1

Abstract

Oculocutaneous albinism type 1 is a rare autosomal recessive disorder caused by pathogenic variants in the tyrosinase (TYR) gene, resulting in impaired melanin synthesis and characteristic cutaneous and ocular manifestations. This study aimed to investigate the molecular basis of oculocutaneous albinism type 1 in a consanguineous family through clinical evaluation, molecular genetic analysis, and bioinformatics approaches. Three affected male siblings from a consanguineous family underwent detailed clinical assessment. Genomic DNA was isolated from peripheral blood samples, and one affected individual was analyzed by whole exome sequencing (WES) to identify the disease-causing variants. Variant segregation within the family was confirmed by Sanger sequencing, while pathogenicity and evolutionary conservation were evaluated using established bioinformatics tools. Clinical examination revealed generalized hypopigmentation, white hair, photophobia, congenital nystagmus, and reduced visual acuity. A homozygous pathogenic missense variant, c.1255G>A (p.Gly419Arg) in the TYR gene, was identified and showed complete segregation with the disease phenotype. Bioinformatics analyses predicted the variant to be deleterious and demonstrated that the affected amino acid residue is highly conserved across vertebrate species. These findings provide molecular confirmation of a recurrent pathogenic TYR variant and expand the available genetic data for an underrepresented population, highlighting the importance of molecular diagnosis and genetic counselling in communities with a high prevalence of consanguineous marriages.