We identified a common polymorphism in contactin-associated protein-like 2 (CNTNAP2), a member of the neurexin superfamily, that is significantly associated with autism susceptibility.
We identified a common polymorphism in contactin-associated protein-like 2 (CNTNAP2), a member of the neurexin superfamily, that is significantly associated with autism susceptibility.
We focused our initial analysis on CNTNAP2 based on our demonstration of disruption of Contactin 4 (CNTN4) in a patient with ASD; the recent finding of rare homozygous mutations in CNTNAP2 leading to intractable seizures and autism; and in situ and biochemical analyses reported herein that confirm expression in relevant brain regions and demonstrate the presence of CNTNAP2 in the synaptic plasma membrane fraction of rat forebrain lysates.
We aimed to elucidate the genetic association of CNTNAP2 within high functioning ASD (HFA), focusing on autism specific symptoms and reducing intelligence related factors.
Using immunofluorescence confocal microscopy and complementary biochemical techniques, we compared wild-type CASPR2 to 12 point mutations identified in individuals with autism.
Two genes, CNTNAP2 and NOBOX, both contained within the deletion region, have been recently associated with autism susceptibility and premature ovarian failure, respectively.
Together, these results provide convergent evidence for involvement of CNTNAP2, a Neurexin family member, in autism, and demonstrate a connection between genetic risk for autism and specific brain structures.
These findings reveal a key contribution of ASD-associated gene CNTNAP2 in modulating macroscale functional connectivity, and suggest that homozygous loss-of-function mutations in this gene may predispose to neurodevelopmental disorders and autism through a selective dysregulation of connectivity in integrative prefrontal areas.
The convergence between genetic findings and cognitive-behavioral models of autism provides evidence that genetic variation at CNTNAP2 predisposes to diseases such as autism in part through modulation of frontal lobe connectivity.
The CNTNAP2 (contactin-associated protein-like 2) gene, highly expressed in the human prefrontal cortex, has been linked with autism and language impairment.
Polymorphisms of CNTNAP2 (contactin-associated like protein-2), a member of the neurexin family, have already been implicated as a susceptibility gene for autism by at least 3 separate studies.
One such gene is CNTNAP2 encoding contactin-associated protein 2 (CASPR2), which harbours mutations associated to autism, schizophrenia, and intellectual disability.
No evidence for association of autism with rare heterozygous point mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contactin-Associated Proteins or Contactins.
Mutations in the contactin-associated protein 2 (CNTNAP2) gene encoding CASPR2, a neurexin-related cell-adhesion molecule, predispose to autism, but the function of CASPR2 in neural circuit assembly remains largely unknown.
In this issue of AJHG, Alarcón et al.,(1) Arking et al.,(2) and Bakkaloglu et al.(3) identify a series of functional variants in the CNTNAP2 gene that unequivocally implicate this gene as causing Type 1 autism in the general population.
In the current study we investigated the functional effects of variants of CNTNAP2 associated with autism and language impairment (rs7794745 and rs2710102; presumed risk alleles T and C, respectively) in healthy individuals using functional magnetic resonance imaging (fMRI) during performance of a language task (n = 66).
In mice lacking the autism-associated gene Cntnap2, both the categorization of sensory stimuli and the refinement of social representations were impaired.