CETN3 Deficiency Induces Microcephaly by Disrupting NPC Cell Fate through Impaired Centrosome Assembly and RNA Splicing

ABSTRACT: Primary microcephaly, a rare congenital condition characterized by reduced brain size, occurs due to impaired neurogenesis during brain development. Through whole exome sequencing, we identified compound heterozygous loss-of-function mutations in CENTRIN 3 (CETN3) in a 5-year-old patient with primary microcephaly. As CETN3 has not been previously linked to microcephaly, we investigated its potential function in neurodevelopment in human pluripotent stem cell-derived cerebral organoids. We showed that CETN3-knockout (KO) organoids successfully recapitulated the microcephaly phenotype of reduced size compared to the control organoids. Through transcriptomic, histological, and protein analyses, we found that CETN3 deficiency directly interferes with neuronal differentiation and reduces prolif

SUBMITTER: Jing Xu 

PROVIDER: S-SCDT-10_1038-S44321-025-00302-7 | biostudies-other |

REPOSITORIES: biostudies-other