Relevance to Autism

Several de novo coding variants in the CDH2 gene, including a de novo missense variant that was predicted to be damaging, have been identified in ASD probands (Iossifov et al., 2014; Takata et al., 2018; Zhou et al., 2022; Miyake et al., 2023). Accogli et al., 2019 reported nine individuals with de novo heterozygous variants in the CDH2 gene presenting with a syndromic neurodevelopmental disorder characterized by global developmental delay and/or intellectual disability, variable axon pathfinding defects, ocular, cardiac, and genital anomalies; five of the de novo CDH2 missense variants identified in this report, including two that were identified in individuals who were reported to have autism, were experimentally shown to result in impaired cell-cell adhesion. A homozygous missense variant in the CDH2 gene (p.His150Tyr) was identified in three siblings born to consanguineous Bedouin parents who met DSM-5 criteria for ADHD; one of these individuals also presented with mild developmental delay and autism spectrum disorder (Halperin et al., 2021). Additional functional studies in Halperin et al., 2021 using a CRISPR/Cas9-mutated knock-in mice harboring the CHD2 p.His150Tyr variant in the mouse ortholog recapitulated core behavioral features of hyperactivity; mutant mice also exhibited impaired pre-synaptic vesicle clustering, attenuated evoked transmitted release, and decreased spontaneous release. Rare missense variants in the CDH2 gene have been identified in probands with obsessive-compulsive behavior (OCD) and Tourette syndrome (Moya et al., 2013).

Molecular Function

This gene encodes a classical cadherin and member of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein is proteolytically processed to generate a calcium-dependent cell adhesion molecule and glycoprotein. This protein plays a role in the establishment of left-right asymmetry, development of the nervous system and the formation of cartilage and bone.

External Links

References