Distinct pathophysiological mechanisms of CEP152 variants in microcephaly and brain abnormalities

ABSTRACT: CEP152 is essential for centriole function and neurodevelopment, and pathogenic recessive variants in CEP152 cause primary microcephaly. We identified new compound heterozygous CEP152 variants, c.314G>A,p.(W105*) and c.2689A>T,p.(K897*), in a microcephalic patient and analyzed them alongside a homozygous variant c.95A>C,p.(Q32P) associated with severe microcephaly with marked gyral simplification. In vitro assays revealed distinct effects: p.K897* prevented centrosomal localization, p.W105* led to protein degradation, and p.Q32P retained centrosomal targeting but disrupted binding to Polo-like kinase 4, a key centriole biogenesis kinase and CEP152 partner. In vivo, both Cep152W105*/K897* and Cep152Q32P/Q32P knock-in mice displayed microcephaly; notably, Cep152Q32P/Q32P mice also e

SUBMITTER: Nanako Hamada 

PROVIDER: S-SCDT-10_1038-S44321-026-00427-3 | biostudies-other |

REPOSITORIES: biostudies-other