Disruption of CTNND2, encoding delta-catenin, causes a penetrant attention deficit disorder and myopia
Abidemi Adegbola,
Richard Lutz,
Elina Nikkola,
Samuel P. Strom,
Jonathan Picker,
Anthony Wynshaw-Boris
Affiliations
Abidemi Adegbola
Department of Psychiatry, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, OH 44106, USA; Department of Genetics and Genome Sciences and Center for Human Genetics, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, OH 44106, USA; Corresponding author
Richard Lutz
Department of Genetic Medicine, Munroe Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE 68198, USA
Elina Nikkola
Fulgent Genetics, Temple City, CA 91780, USA
Samuel P. Strom
Fulgent Genetics, Temple City, CA 91780, USA
Jonathan Picker
Division of Genetics and Genomics, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Child and Adolescent Psychiatry, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Anthony Wynshaw-Boris
Department of Genetics and Genome Sciences and Center for Human Genetics, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, OH 44106, USA
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.
