What does CNTNAP2 reveal about autism spectrum disorder?

Abstract

Autism spectrum disorder (ASD) is a phenotypically and genetically heterogeneous condition characterized by the presence of repetitive/restrictive behaviors and variable deficits in language and social behavior. Many genes predisposing an individual to ASD have been identified, and understanding the causal disease mechanism(s) is critical to be able to develop treatments. Neurobiological, genetic, and imaging data provide strong evidence for the CNTNAP2 gene as a risk factor for ASD and related neurodevelopmental disorders. This review discusses the clinical genetics and current understanding of the biology of CNTNAP2 as related to ASD and illustrates how the integration of multiple research approaches, from human studies to animal models, converge to inform functional biology focused on novel treatment development.

Figure 1. Schematic representation of the location of the mutations/variants found within CNTNAP2 associated to neurodevelopmental disorders

The CNTNAP2 gene spans 2.3 Mb on chromosome 7. Exons are presented as numbered dark blue boxes, introns as a light blue line. Variants from references listed in Table 1 are indicated on top. The protein structural domains encoded by the specific exons are presented at the bottom. SP, signal peptide; FA58C, coagulation factor 5/8 C-terminal domain; LamG, laminin G; EGF, epidermal growth factor; FBG, fibrinogen-like domain; TM, transmembrane domain; 4.1, protein 4.1B binding domain; PDZ, PSD95/DlgA/ZO-1 homology protein-protein interaction domain.

Figure 2. Genetic contribution of CNTNAP2 to Autism Spectrum Disorders

CNTNAP2 is expressed in brain regions important for social cognition, language and implicit learning such as the frontal cortex (red), the anterior temporal cortex (blue) and the basal ganglia (green). Its contribution to the clinical phenotype is seen as an influence on the development and function of these brain circuits.