CRB1 gene variant in leber congenital amaurosis: molecular and clinical investigations

In Iran, due to widespread consanguineous marriages, the emergence of genetic variants is a likely issue. This study aimed to describe an Iranian female patient with a novel variant in the Crumbs homologue 1 (CRB1) associated with Leber congenital amaurosis (LCA). A novel variation of the CRB1 gene was identified by Exome-Sequencing and Sanger Sequencing. The bioinformatics analysis was employed to assess the pathogenicity criteria of the variant and the variation in expressed proteins. We identified a novel homozygous nonsense variant in the CRB1 gene (c.2106T > G; p.Tyr702*) in a 28-year-old woman born to a consanguineous marriage. The patient presented with severe early-onset visual impairment consistent with Leber congenital amaurosis, characterized by progressive loss of central and peripheral vision, nyctalopia, and visual field constriction. Bioinformatic analyses supported the pathogenicity of the identified variant, which is predicted to result in a truncated CRB1 protein and loss of function. This study elucidates the LCA genotype linked to CRB1 in patients, significantly enhancing diagnostic precision and facilitating informed treatment choices.