Association of Mouse Dlg4 (PSD-95) Gene Deletion and Human DLG4 Gene Variation With Phenotypes Relevant to Autism Spectrum Disorders and Williams' Syndrome
- Michael Feyder,
B.S. , - Rose-Marie Karlsson,
Ph.D. , - Poonam Mathur,
B.S. , - Matthew Lyman,
B.S. , - Roland Bock,
M.Sc. , - Reza Momenan,
Ph.D. , - Jeeva Munasinghe,
Ph.D. , - Maria Luisa Scattoni,
Ph.D. , - Jessica Ihne,
B.S. , - Marguerite Camp,
Ph.D. , - Carolyn Graybeal,
B.A. , - Douglas Strathdee,
Ph.D. , - Alison Begg,
Ph.D. , - Veronica A. Alvarez,
Ph.D. , - Peter Kirsch,
Ph.D. , - Marcella Rietschel,
M.D. , - Sven Cichon,
Ph.D. , - Henrik Walter,
M.D., Ph.D. , - Andreas Meyer-Lindenberg,
M.D., Ph.D. , - Seth G.N. Grant,
B.Sc., M.B.B.S. , and - Andrew Holmes,
Ph.D.
From the Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA); Section on Synaptic Pharmacology and Section on Neuronal Structure, Laboratory for Integrative Neuroscience, NIAAA; Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, NIAAA; National Institute of Neurological Disorders and Stroke; Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit…, Rome; Wellcome Trust Sanger Institute, Well-come Trust Genome Campus, Hinxton, U.K.; Centre for Neuroscience, University of Edinburgh, Edinburgh; Department of Psychiatry and Psychotherapy and Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany; Department of Genomics, Life and Brain Center, and Institute of Human Genetics, and Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
From the Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA); Section on Synaptic Pharmacology and Section on Neuronal Structure, Laboratory for Integrative Neuroscience, NIAAA; Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, NIAAA; National Institute of Neurological Disorders and Stroke; Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit…, Rome; Wellcome Trust Sanger Institute, Well-come Trust Genome Campus, Hinxton, U.K.; Centre for Neuroscience, University of Edinburgh, Edinburgh; Department of Psychiatry and Psychotherapy and Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany; Department of Genomics, Life and Brain Center, and Institute of Human Genetics, and Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
From the Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA); Section on Synaptic Pharmacology and Section on Neuronal Structure, Laboratory for Integrative Neuroscience, NIAAA; Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, NIAAA; National Institute of Neurological Disorders and Stroke; Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit…, Rome; Wellcome Trust Sanger Institute, Well-come Trust Genome Campus, Hinxton, U.K.; Centre for Neuroscience, University of Edinburgh, Edinburgh; Department of Psychiatry and Psychotherapy and Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany; Department of Genomics, Life and Brain Center, and Institute of Human Genetics, and Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
From the Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA); Section on Synaptic Pharmacology and Section on Neuronal Structure, Laboratory for Integrative Neuroscience, NIAAA; Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, NIAAA; National Institute of Neurological Disorders and Stroke; Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit…, Rome; Wellcome Trust Sanger Institute, Well-come Trust Genome Campus, Hinxton, U.K.; Centre for Neuroscience, University of Edinburgh, Edinburgh; Department of Psychiatry and Psychotherapy and Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany; Department of Genomics, Life and Brain Center, and Institute of Human Genetics, and Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
From the Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA); Section on Synaptic Pharmacology and Section on Neuronal Structure, Laboratory for Integrative Neuroscience, NIAAA; Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, NIAAA; National Institute of Neurological Disorders and Stroke; Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit…, Rome; Wellcome Trust Sanger Institute, Well-come Trust Genome Campus, Hinxton, U.K.; Centre for Neuroscience, University of Edinburgh, Edinburgh; Department of Psychiatry and Psychotherapy and Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany; Department of Genomics, Life and Brain Center, and Institute of Human Genetics, and Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
From the Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA); Section on Synaptic Pharmacology and Section on Neuronal Structure, Laboratory for Integrative Neuroscience, NIAAA; Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, NIAAA; National Institute of Neurological Disorders and Stroke; Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit…, Rome; Wellcome Trust Sanger Institute, Well-come Trust Genome Campus, Hinxton, U.K.; Centre for Neuroscience, University of Edinburgh, Edinburgh; Department of Psychiatry and Psychotherapy and Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany; Department of Genomics, Life and Brain Center, and Institute of Human Genetics, and Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
From the Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA); Section on Synaptic Pharmacology and Section on Neuronal Structure, Laboratory for Integrative Neuroscience, NIAAA; Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, NIAAA; National Institute of Neurological Disorders and Stroke; Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit…, Rome; Wellcome Trust Sanger Institute, Well-come Trust Genome Campus, Hinxton, U.K.; Centre for Neuroscience, University of Edinburgh, Edinburgh; Department of Psychiatry and Psychotherapy and Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany; Department of Genomics, Life and Brain Center, and Institute of Human Genetics, and Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
From the Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA); Section on Synaptic Pharmacology and Section on Neuronal Structure, Laboratory for Integrative Neuroscience, NIAAA; Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, NIAAA; National Institute of Neurological Disorders and Stroke; Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit…, Rome; Wellcome Trust Sanger Institute, Well-come Trust Genome Campus, Hinxton, U.K.; Centre for Neuroscience, University of Edinburgh, Edinburgh; Department of Psychiatry and Psychotherapy and Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany; Department of Genomics, Life and Brain Center, and Institute of Human Genetics, and Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
From the Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA); Section on Synaptic Pharmacology and Section on Neuronal Structure, Laboratory for Integrative Neuroscience, NIAAA; Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, NIAAA; National Institute of Neurological Disorders and Stroke; Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit…, Rome; Wellcome Trust Sanger Institute, Well-come Trust Genome Campus, Hinxton, U.K.; Centre for Neuroscience, University of Edinburgh, Edinburgh; Department of Psychiatry and Psychotherapy and Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany; Department of Genomics, Life and Brain Center, and Institute of Human Genetics, and Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
From the Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA); Section on Synaptic Pharmacology and Section on Neuronal Structure, Laboratory for Integrative Neuroscience, NIAAA; Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, NIAAA; National Institute of Neurological Disorders and Stroke; Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit…, Rome; Wellcome Trust Sanger Institute, Well-come Trust Genome Campus, Hinxton, U.K.; Centre for Neuroscience, University of Edinburgh, Edinburgh; Department of Psychiatry and Psychotherapy and Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany; Department of Genomics, Life and Brain Center, and Institute of Human Genetics, and Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
From the Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA); Section on Synaptic Pharmacology and Section on Neuronal Structure, Laboratory for Integrative Neuroscience, NIAAA; Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, NIAAA; National Institute of Neurological Disorders and Stroke; Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit…, Rome; Wellcome Trust Sanger Institute, Well-come Trust Genome Campus, Hinxton, U.K.; Centre for Neuroscience, University of Edinburgh, Edinburgh; Department of Psychiatry and Psychotherapy and Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany; Department of Genomics, Life and Brain Center, and Institute of Human Genetics, and Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
From the Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA); Section on Synaptic Pharmacology and Section on Neuronal Structure, Laboratory for Integrative Neuroscience, NIAAA; Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, NIAAA; National Institute of Neurological Disorders and Stroke; Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit…, Rome; Wellcome Trust Sanger Institute, Well-come Trust Genome Campus, Hinxton, U.K.; Centre for Neuroscience, University of Edinburgh, Edinburgh; Department of Psychiatry and Psychotherapy and Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany; Department of Genomics, Life and Brain Center, and Institute of Human Genetics, and Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
From the Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA); Section on Synaptic Pharmacology and Section on Neuronal Structure, Laboratory for Integrative Neuroscience, NIAAA; Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, NIAAA; National Institute of Neurological Disorders and Stroke; Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit…, Rome; Wellcome Trust Sanger Institute, Well-come Trust Genome Campus, Hinxton, U.K.; Centre for Neuroscience, University of Edinburgh, Edinburgh; Department of Psychiatry and Psychotherapy and Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany; Department of Genomics, Life and Brain Center, and Institute of Human Genetics, and Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
From the Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA); Section on Synaptic Pharmacology and Section on Neuronal Structure, Laboratory for Integrative Neuroscience, NIAAA; Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, NIAAA; National Institute of Neurological Disorders and Stroke; Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit…, Rome; Wellcome Trust Sanger Institute, Well-come Trust Genome Campus, Hinxton, U.K.; Centre for Neuroscience, University of Edinburgh, Edinburgh; Department of Psychiatry and Psychotherapy and Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany; Department of Genomics, Life and Brain Center, and Institute of Human Genetics, and Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
From the Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA); Section on Synaptic Pharmacology and Section on Neuronal Structure, Laboratory for Integrative Neuroscience, NIAAA; Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, NIAAA; National Institute of Neurological Disorders and Stroke; Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit…, Rome; Wellcome Trust Sanger Institute, Well-come Trust Genome Campus, Hinxton, U.K.; Centre for Neuroscience, University of Edinburgh, Edinburgh; Department of Psychiatry and Psychotherapy and Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany; Department of Genomics, Life and Brain Center, and Institute of Human Genetics, and Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
From the Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA); Section on Synaptic Pharmacology and Section on Neuronal Structure, Laboratory for Integrative Neuroscience, NIAAA; Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, NIAAA; National Institute of Neurological Disorders and Stroke; Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit…, Rome; Wellcome Trust Sanger Institute, Well-come Trust Genome Campus, Hinxton, U.K.; Centre for Neuroscience, University of Edinburgh, Edinburgh; Department of Psychiatry and Psychotherapy and Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany; Department of Genomics, Life and Brain Center, and Institute of Human Genetics, and Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
From the Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA); Section on Synaptic Pharmacology and Section on Neuronal Structure, Laboratory for Integrative Neuroscience, NIAAA; Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, NIAAA; National Institute of Neurological Disorders and Stroke; Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit…, Rome; Wellcome Trust Sanger Institute, Well-come Trust Genome Campus, Hinxton, U.K.; Centre for Neuroscience, University of Edinburgh, Edinburgh; Department of Psychiatry and Psychotherapy and Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany; Department of Genomics, Life and Brain Center, and Institute of Human Genetics, and Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
From the Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA); Section on Synaptic Pharmacology and Section on Neuronal Structure, Laboratory for Integrative Neuroscience, NIAAA; Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, NIAAA; National Institute of Neurological Disorders and Stroke; Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit…, Rome; Wellcome Trust Sanger Institute, Well-come Trust Genome Campus, Hinxton, U.K.; Centre for Neuroscience, University of Edinburgh, Edinburgh; Department of Psychiatry and Psychotherapy and Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany; Department of Genomics, Life and Brain Center, and Institute of Human Genetics, and Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
From the Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA); Section on Synaptic Pharmacology and Section on Neuronal Structure, Laboratory for Integrative Neuroscience, NIAAA; Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, NIAAA; National Institute of Neurological Disorders and Stroke; Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit…, Rome; Wellcome Trust Sanger Institute, Well-come Trust Genome Campus, Hinxton, U.K.; Centre for Neuroscience, University of Edinburgh, Edinburgh; Department of Psychiatry and Psychotherapy and Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany; Department of Genomics, Life and Brain Center, and Institute of Human Genetics, and Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
From the Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA); Section on Synaptic Pharmacology and Section on Neuronal Structure, Laboratory for Integrative Neuroscience, NIAAA; Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, NIAAA; National Institute of Neurological Disorders and Stroke; Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit…, Rome; Wellcome Trust Sanger Institute, Well-come Trust Genome Campus, Hinxton, U.K.; Centre for Neuroscience, University of Edinburgh, Edinburgh; Department of Psychiatry and Psychotherapy and Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany; Department of Genomics, Life and Brain Center, and Institute of Human Genetics, and Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
From the Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA); Section on Synaptic Pharmacology and Section on Neuronal Structure, Laboratory for Integrative Neuroscience, NIAAA; Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, NIAAA; National Institute of Neurological Disorders and Stroke; Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit…, Rome; Wellcome Trust Sanger Institute, Well-come Trust Genome Campus, Hinxton, U.K.; Centre for Neuroscience, University of Edinburgh, Edinburgh; Department of Psychiatry and Psychotherapy and Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany; Department of Genomics, Life and Brain Center, and Institute of Human Genetics, and Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
Abstract
Objective:
Research is increasingly linking autism spectrum disorders and other neurodevelopmental disorders to synaptic abnormalities (“synaptopathies”). PSD-95 (postsynaptic density-95, DLG4) orchestrates protein-protein interactions at excitatory synapses and is a major functional bridge interconnecting a neurexinneuroligin-SHANK pathway implicated in autism spectrum disorders.
Method:
The authors characterized behavioral, dendritic, and molecular phenotypic abnormalities relevant to autism spectrum disorders in mice with PSD-95 deletion (Dlg4−/−). The data from mice led to the identification of single-nucleotide polymorphisms (SNPs) in human DLG4 and the examination of associations between these variants and neural signatures of Williams' syndrome in a normal population, using functional and structural neuroimaging.
Results:
Dlg4−/− showed increased repetitive behaviors, abnormal communication and social behaviors, impaired motor coordination, and increased stress reactivity and anxiety-related responses. Dlg4−/− had subtle dysmorphology of amygdala dendritic spines and altered forebrain expression of various synaptic genes, including Cyln2, which regulates cytoskeletal dynamics and is a candidate gene for Williams' syndrome. A signifi-cant association was observed between variations in two human DLG4 SNPs and reduced intraparietal sulcus volume and abnormal cortico-amygdala coupling, both of which characterize Williams' syndrome.
Conclusions:
These findings demonstrate that DLG4 gene disruption in mice produces a complex range of behavioral and molecular abnormalities relevant to autism spectrum disorders and Williams' syndrome. The study provides an initial link between human DLG4 gene variation and key neural endophenotypes of Williams' syndrome and perhaps corticoamygdala regulation of emotional and social processes more generally.