Table 3 Phenotypic analyses of ASD iPSC-derived neurons : Rett, Phelan-Mcdermid, Timothy, Fragile-X, and Angelman Syndromes

Rett syndrome

Methyl CpG binding protein 2 (MECP2)

Embryoid body formation

Gluramatergic & gabaergic neurons

Reduced sEPSC and sIPSC

Fewer synaptic conracts; reduced cell soma size and dendritic branching and spine density

Marchetto et al. 2010 [104]; Cheung et al. 2011 [105]; Kim et al. 2011 [106]

Phelan-McDermid Syndrome (PMDS) (22q13 deletion syndrome)

Shank3

Dual smad inhibition

Forebrain neurons

Reduced excitatory synaptic transmission

Reduced glutamatergic receptors; decreased number of synapses

Shcheglovitov et al. 2013 [117]

Timothy syndrome (A member of the long QT syndromes)

CACNA1 (alpha-1 subunit of the L-type calcium channel CaV1.2)

Embryoid body formation

Cortical-enriched neuronal populations

Increase in the sustained intracellular calcium rise following membrane depolarization; wider action potentials

Decreased expression of lower corticallayers-related genes; increases in TH (tyrosine hydroxylase)-, norepinephrine- and dopamine-positice cells; activity-dependent dendrite retraction

Pasca et al. 2011 [107]; Krey et al. 2013 [108]

Fragile X syndrome

Fragile X mental retardation 1 (FMR1)

Embryoid body formation

Tuj1-, MAP2- or GFAP-positive cells

Poor spontaneous synaptic activity and no glutamate reactivity

Reduced neurite numbers and neurite lengths; reduced PSD95 protein expression and reduced synaptic punctadensity; poor neuronal maturation and high gliogenic development

Sheridan et al. 2011 [109]; Telias et al. 2013 [110]

Angelman syndrome

Ubiquitin protein ligase E3A (UBE3A)

Embryoid body formation

Tuj1-positive cells

Normal electrophysiological properties

Intact imprinting of UBE3A

Chamberlain et al. 2010 [111]