CUL1 variants cause severe neurodevelopmental disorders: Insights from human genetics and a zebrafish model of microcephaly.

ABSTRACT: Microcephaly is a neurodevelopmental anomaly characterized by reduced head circumference and impaired brain growth, often accompanied by intellectual disability (ID), developmental delays, and seizures. While numerous genes have been implicated in microcephaly, the role of the SCF (Skp1-Cul1-F-box protein) ubiquitin ligase complex, particularly its core component CUL1, remains poorly understood. In this study, we identified heterozygous de novo and inherited variants in the CUL1 gene in four unrelated families with severe microcephaly, ID, and developmental delays. To investigate the functional consequences of CUL1 loss of function, we developed a zebrafish model with knockdown of cul1a&b, which exhibited significant reductions in central nervous system size and behavioral defects, mirrori

SUBMITTER: Xu H 

PROVIDER: S-EPMC12704061 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature