Pathogenicity of Mediator Complex Subunit 27 (MED27) in a Neurodevelopmental Disorder with Cerebellar Atrophy.

ABSTRACT: Neurodevelopmental disorders (NDDs) affect brain function and development, with 90% lacking approved treatments. Understanding their pathogenic mechanisms is critical for developing precision gene therapies. An autosomal recessive NDD associated with variants in the Mediator complex subunit 27 (MED27) gene is previously identified. The Mediator complex is essential for transcription initiation by bridging transcription factors (TFs) at enhancers to RNA polymerase II at promoters. All patients with MED27 variants exhibit cerebellar hypoplasia or atrophy, underscoring the cerebellum's heightened vulnerability to MED27 dysfunction. To investigate the disease mechanisms, in vitro stem cells carrying patient-specific MED27 variants and in vivo mouse models with Med27 loss-of-function (LoF) are

SUBMITTER: Yiliyaer N 

PROVIDER: S-EPMC12752580 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature