title: Copy number variation analysis in adults with catatonia confirms haploinsufficiency of SHANK3 as a predisposing factor.
abstract: BACKGROUND
  Catatonia is a motor dysregulation syndrome co-occurring with a variety of psychiatric and medical disorders. Response to treatment with benzodiazepines and electroconvulsive therapy suggests a neurobiological background. The genetic etiology however remains largely unexplored. Copy Number Variants (CNV), known to predispose to neurodevelopmental disorders, may play a role in the etiology of catatonia.
  
  
  METHODS
  This study is exploring the genetic field of catatonia through CNV analysis in a cohort of psychiatric patients featuring intellectual disability and catatonia. Fifteen adults admitted to a psychiatric inpatient unit and diagnosed with catatonia were selected for array Comparative Genomic Hybridization analysis at 200 kb resolution. We introduced a CNV interpretation algorithm to define detected CNVs as benign, unclassified, likely pathogenic or causal with regard to catatonia.
  
  
  RESULTS
  Co-morbid psychiatric diagnoses in these patients were autism, psychotic or mood disorders. Eight patients were found to carry rare CNVs, which could not be classified as benign, comprising 6 duplications and 2 deletions. Microdeletions on 22q13.3, considered causal for catatonia, were detected in 2 patients. Duplications on 16p11.2 and 22q11.2 were previously implicated in psychiatric disorders, but not in catatonia, and were therefore considered likely pathogenic. Driven by the identification of a rare 14q11.2 duplication in one catatonic patient, additional patients with overlapping duplications were gathered to delineate a novel susceptibility locus for intellectual disability and psychiatric disorders on 14q11.2, harboring the gene SUPT16H. Three remaining variants respectively on 2q36.1, 16p13.13 and 17p13.3 were considered variants of unknown significance.
  
  
  CONCLUSIONS
  The identification of catatonia-related copy number changes in this study, underscores the importance of genetic research in patients with catatonia. We confirmed that 22q13.3 deletions, affecting the gene SHANK3, predispose to catatonia, and we uncover 14q11.2 duplications as a novel susceptibility factor for intellectual and psychiatric disorders.
authors: Center for Human Genetics, Catholic University Leuven, Leuven, Belgium.
authors: Jeroen
authors: J
authors: Breckpot
authors: University Psychiatric Center KU Leuven, Catholic University of Leuven, Belgium.
authors: Marieke
authors: M
authors: Vercruyssen
authors: St-Camillus Psychiatric Hospital, Bierbeek, Belgium.
authors: Eddy
authors: E
authors: Weyts
authors: St-Camillus Psychiatric Hospital, Bierbeek, Belgium.
authors: Sean
authors: S
authors: Vandevoort
authors: St-Camillus Psychiatric Hospital, Bierbeek, Belgium.
authors: Greet
authors: G
authors: D'Haenens
authors: Center for Human Genetics, Catholic University Leuven, Leuven, Belgium.
authors: Griet
authors: G
authors: Van Buggenhout
authors: University Psychiatric Center KU Leuven, Catholic University of Leuven, Belgium.
authors: Lore
authors: L
authors: Leempoels
authors: Center for Human Genetics, Franche-Comté University, Besançon, France.
authors: Elise
authors: E
authors: Brischoux-Boucher
authors: Center for Human Genetics, Franche-Comté University, Besançon, France.
authors: Lionel
authors: L
authors: Van Maldergem
authors: Medical Genetics, University of Siena, Policlinico Le Scotte, Siena, Italy; Medical Genetics, Azienda University Hospital, Siena, Italy.
authors: Alessandra
authors: A
authors: Renieri
authors: Medical Genetics, Azienda University Hospital, Siena, Italy.
authors: Maria Antonietta
authors: MA
authors: Mencarelli
authors: Human Genome and Stem Cell Center, University of Sao Paulo, Sao Paulo, Brazil.
authors: Carla
authors: C
authors: D'Angelo
authors: Institute of Maternal and Child Research, Faculty of Medicine, University of Chile, Santiago, Chile.
authors: Veronica
authors: V
authors: Mericq
authors: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Mariette J
authors: MJ
authors: Hoffer
authors: Endocrinology Unit, Children's Hospital, CHU Toulouse, Reference Center for Prader-Willi Syndrome, INSERM UMR 1043, Paul Sabatier University, Toulouse, France.
authors: Maithé
authors: M
authors: Tauber
authors: Endocrinology Unit, Children's Hospital, CHU Toulouse, Reference Center for Prader-Willi Syndrome, INSERM UMR 1043, Paul Sabatier University, Toulouse, France. Electronic address: molinas.c@chu-toulouse.fr.
authors: Catherine
authors: C
authors: Molinas
authors: Unit of Neurology, Department of Pediatric Neurology, Clínica las Condes, Santiago, Chile.
authors: Claudia
authors: C
authors: Castiglioni
authors: Center for Human Genetics, Catholic University Leuven, Leuven, Belgium.
authors: Nathalie
authors: N
authors: Brison
authors: Center for Human Genetics, Catholic University Leuven, Leuven, Belgium.
authors: Joris R
authors: JR
authors: Vermeesch
authors: University Psychiatric Center KU Leuven, Catholic University of Leuven, Belgium.
authors: Marina
authors: M
authors: Danckaerts
authors: University Psychiatric Center KU Leuven, Catholic University of Leuven, Belgium.
authors: Pascal
authors: P
authors: Sienaert
authors: Center for Human Genetics, Catholic University Leuven, Leuven, Belgium.
authors: Koenraad
authors: K
authors: Devriendt
authors: Center for Human Genetics, Catholic University Leuven, Leuven, Belgium. Electronic address: annick.vogels@uzleuven.be.
authors: Annick
authors: A
authors: Vogels
mesh_terms: D000293:Adolescent; D002389:Catatonia / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002883:Chromosomes, Human, Pair 14; D002892:Chromosomes, Human, Pair 22; D056915:DNA Copy Number Variations; D005260:Female; D020022:Genetic Predisposition to Disease; D057895:Haploinsufficiency / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D009419:Nerve Tissue Proteins; C492357:SHANK3 protein, human
keywords: 14q11.2 duplication; Catatonia; Psychiatric disorder; SHANK3; SUPT16H