Models of Bosch-Boonstra-Schaaf optic atrophy syndrome reveal genotype-phenotype correlations in brain structure and behavior.

ABSTRACT: Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is a rare, autosomal dominant neurodevelopmental disorder caused by pathogenic variants in NR2F1, characterized by developmental delay, intellectual disability, optic nerve anomalies and autism spectrum disorder. Most pathogenic variants cluster within the highly conserved DNA-binding domain (DBD) or ligand-binding domain (LBD) of NR2F1 and are associated with variable clinical severity, suggesting a genotype-phenotype correlation. Although previous mouse models have provided important insights, comprehensive behavioral characterization remains limited. Here, we present two novel BBSOAS mouse models harboring patient-specific variants in the DBD (Nr2f1+/R139L) and LBD (Nr2f1+/E397*), alongside the established Nr2f1+/- model. We analyzed

SUBMITTER: Maass JG 

PROVIDER: S-EPMC12505268 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature