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Disruption of CTNND2, encoding delta-catenin, causes a penetrant attention deficit disorder and myopia
Abidemi Adegbola1,2, Richard Lutz3, Elina Nikkola4
1Department of Psychiatry, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, OH 44106, USA.
Abstract:
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.
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