FBXO22 deficiency defines a pleiotropic syndrome of growth restriction and multi-system anomalies associated with a unique epigenetic signature.

ABSTRACT: FBXO22 encodes an F-box protein, which acts as a substrate-recognition component of the SKP1-CUL1-F-box (SCF) E3 ubiquitin ligase complex. Despite its known roles in the post-translational ubiquitination and degradation of specific substrates, including histone demethylases, the impact of FBXO22 on human development remains unknown. Here, we characterize a pleiotropic syndrome with prominent prenatal onset growth restriction and notable neurodevelopmental delay across 16 cases from 14 families. Through exome and genome sequencing, we identify four distinct homozygous FBXO22 variants with loss-of-function effects segregating with the disease: three predicted to lead to premature translation termination due to frameshift effects and a single-amino-acid-deletion variant, which, we show, impac

SUBMITTER: Ramakrishna NB 

PROVIDER: S-EPMC12120182 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature