RESUMEN
Mutations to genes that encode DNA-binding transcription factors (TFs) underlie a broad spectrum of human neurodevelopmental disorders. Here, we highlight the pathological mechanisms arising from mutations to TF genes that influence the development of mammalian cerebral cortex neurons. Drawing on recent findings for TF genes including ZBTB18, we discuss how functional missense mutations to such genes confer non-native gene regulatory actions in developing neurons, leading to cell-morphological defects, neuroanatomical abnormalities during foetal brain development and functional impairment. Further, we discuss how missense variation to human TF genes documented in the general population endow quantifiable changes to transcriptional regulation, with potential cell biological effects on the temporal progression of cerebral cortex neuron development and homeostasis. We offer a systematic approach to investigate the functional impact of missense variation in brain TFs and define their direct molecular and cellular actions in foetal neurodevelopment, tissue homeostasis and disease states.
Asunto(s)
Regulación de la Expresión Génica , Factores de Transcripción , Animales , Humanos , Mamíferos/metabolismo , Mutación , Mutación Missense/genética , Neuronas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
A case of a missense RBM10 variant in an adult with mild to moderate intellectual disability.