A pathogenic NR2F1 gene variant disrupts transcriptional activity and causes severe neurodevelopmental delay in Bosch-Boonstra-Schaaf syndrome.

ABSTRACT:

Introduction

Nuclear receptor subfamily 2, group F, member 1 (NR2F1) gene variations are associated with Bosch-Boonstra-Schaaf optic atrophy syndrome. The NR2F1 genotype correlates with its phenotype; variants within the DNA-binding domain may cause severe psychomotor developmental disorders. However, the mechanisms underlying these phenotypes remain unclear.

Methods

Whole-exome sequencing was performed on the proband and her parents DNA. Candidate variants were verified by Sanger sequencing and bioinformatics analyses. Molecular dynamics simulations were performed to predict structural changes in the mutant NR2F1 protein. A dual-luciferase assay was used to analyze the variant's effect on transcriptional activation.

Results

The proband was a 10-month-old girl with se

SUBMITTER: Liu J 

PROVIDER: S-EPMC11871647 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature