Disruption of CTNND2, encoding delta-catenin, causes a penetrant attention deficit disorder and myopia

• Main Authors: Abidemi Adegbola, Richard Lutz, Elina Nikkola, Samuel P. Strom, Jonathan Picker, Anthony Wynshaw-Boris
• Format: Article
• Language: English
• Published: Elsevier 2020-10-01
• Series: HGG Advances
• Subjects: attention deficit hyperactivity disorder (ADHD); translocation mapping; whole genome sequencing; Nanopore sequencing; familial ADHD; refractive error of the eye
• Online Access: http://www.sciencedirect.com/science/article/pii/S2666247720300075
• ISSN: 2666-2477

Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable neurodevelopmental disorder with poorly understood pathophysiology and genetic mechanisms. A balanced chromosomal translocation interrupts CTNND2 in several members of a family with profound attentional deficit and myopia, and disruption of the gene was found in a separate unrelated individual with ADHD and myopia. CTNND2 encodes a brain-specific member of the adherens junction complex essential for postsynaptic and dendritic development, a site of potential pathophysiology in attentional disorders. Therefore, we propose that the severe and highly penetrant nature of the ADHD phenotype in affected individuals identifies CTNND2 as a potential gateway to ADHD pathophysiology similar to the DISC1 translocation in psychosis or AUTS2 in autism.