MARK2 variants cause autism spectrum disorder via the downregulation of WNT/β-catenin signaling pathway.

ABSTRACT: Microtubule affinity-regulating kinase 2 (MARK2) contributes to establishing neuronal polarity and developing dendritic spines. Although large-scale sequencing studies have associated MARK2 variants with autism spectrum disorder (ASD), the clinical features and variant spectrum in affected individuals with MARK2 variants, early developmental phenotypes in mutant human neurons, and the pathogenic mechanism underlying effects on neuronal development have remained unclear. Here, we report 31 individuals with MARK2 variants and presenting with ASD, other neurodevelopmental disorders, and distinctive facial features. Loss-of-function (LoF) variants predominate (81%) in affected individuals, while computational analysis and in vitro expression assay of missense variants supported the effect of M

SUBMITTER: Gong M 

PROVIDER: S-EPMC11568763 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature