Recent Advances in the Pathogenesis of Syndromic Autisms

Table 3

Candidate genes associated with autism.

Genes	Chromosomes	Proteins	Proteins’ functions	Neurobiological abnormalities	Clinical phenotypes	Refs
NGL3NGL4	Xq13.1Xp22.3	Neuroligin 3/4.	Synaptic transmission, differentiation of synaptic contacts.	Synaptic or dendritic changes.	Autism with motor tics, Mild to severe autism, PDD-NOS, “regression” at disease onset, with a loss of initially-acquired social and verbal milestones, no dysmorphic features.	[79, 80]
SHANK3	22q13	Shank scaffolding proteins.	Master organizer of postsynaptic glutamatergic density.	Synaptic or dendritic changes.	Multiple developmental delays, dysmorphic features, autism with severe language/social deficits.	[81, 82]
MET/HGF	7q31	MET receptortyrosine kinase/hepatocyte growth factor.	Regulation of dendritic morphology and promoting neurite outgrowth.	Abnormalities in development of the cerebral cortex and cerebellum.	Autism, increased anxiety, seizures, immune, and gastrointestinal problems.	[83]
MECP2	Xq28	Methyl-CpG-binding protein 2.	Synapse maintenance and remodeling.	Synaptic or dendritic changes.	Rett syndrome with regression, mental retardation, microcephaly, stereotyped behaviors, epilepsy and breathing problems; verbal Rett variants.	[84]
HOXA1	7p15.3	Homeobox protein.	Regulation of brain growth.	Abnormalities of numbers of neurons or glia in the brain.	Mental retardation, autism and distinct clinical features (horizontal gaze abnormalities, focal weakness, hypoventilation, vascular malformations).	[85]
PTEN	10q23	phosphatase and tensin homologue.	Regulation of cells proliferation/differentiation.	Abnormalities in brain growth.	Macrocephaly, macrosomia, autism and developmental delay, increased risk of developing a variety of PTEN-related cancers in adulthood.	[86, 87]