A novel TYR variant implicated in oculocutaneous albinism type 1 (OCA1): a study in an indigenous population in Southern Brazil

Abstract Background Oculocutaneous albinism (OCA) is a genetic condition with an estimated global prevalence of 1 in 17,000, though this varies across populations. The Kaingang are a Brazilian Indigenous group belonging to the Macro-Jê language family. Objective Report a novel variant TYR :c.704A>G; p. Tyr 235Cys in homozygosity among individuals of Kaingang ethnicity in the state of Rio Grande do Sul, Brazil. Methods A commercial next-generation sequencing (NGS-based) panel for hypopigmentation and oculocutaneous albinism was applied to one saliva sample; exome sequencing (ES) was performed using NGS in another individual; and the remaining 14 individuals were genotyped by quantitative real-time (qPCR). Results The detection of this variant in 14 individuals from the same Indigenous Territory, within an estimated population of 6,000, yields an allele frequency of 0.05, suggesting a founder effect in this population. Discussion/Conclusion The affected individuals were not closely related, suggesting that the recurrence of the variant is not due to recent consanguinity but rather to population structure and inheritance from a common ancestor. In addition, NGS and ES have proven essential for accurate diagnosis of oculocutaneous albinism and for molecular reclassification of cases previously diagnosed clinically. This study contributes to understanding the molecular profile of albinism in Brazilian Indigenous populations, sheds light on historically underrepresented communities in genetic research and has the potential to inform targeted interventions and public health policies for individuals with albinism in these communities.