Chapter 9 - X-Linked ASDs and ID Gene Mutations

Abstract

Intellectual disability (ID) defines a group of disorders that cause impairment in intellectual performance. Autism spectrum disorders (ASDs) cause deficits in communication and social skills in addition to repetitive and stereotyped behaviors. We focus our attention on IDs and ASDs caused by mutations within the X chromosome on genes that exert their roles at the synapse. Notably, a significant overlap exists between ID and ASD in patients, likely mirroring the convergence of molecular pathways by which X-linked gene products regulate brain function. The genes described within are implicated in neuronal morphology, via cytoskeleton remodeling (genes belonging to the Rho GTPase pathway: OPHN1, ARHGEF6, and PAK3), in function, encoding receptor subunits (GRIA3), or acting to localize receptors and secondary messengers (ARHGEF9, TM4SF2, and the MAGUKs CASK and DLG3), and in presynaptic vesicle release (SYP, CASK, and genes belonging to the Rab GTPase pathway: RAB39B and GDI1).