title: Recurrent rearrangements in synaptic and neurodevelopmental genes and shared biologic pathways in schizophrenia, autism, and mental retardation.
abstract: BACKGROUND
  Results of comparative genomic hybridization studies have suggested that rare copy number variations (CNVs) at numerous loci are involved in the cause of mental retardation, autism spectrum disorders, and schizophrenia.
  
  
  OBJECTIVE
  To provide an estimate of the collective frequency of a set of recurrent or overlapping CNVs in 3 different groups of cases compared with healthy control subjects and to assess whether each CNV is present in more than 1 clinical category.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  Academic research.
  
  
  METHODS
  We investigated 28 candidate loci previously identified by comparative genomic hybridization studies for gene dosage alteration in 247 cases with mental retardation, in 260 cases with autism spectrum disorders, in 236 cases with schizophrenia or schizoaffective disorder, and in 236 controls.
  
  
  METHODS
  Collective and individual frequencies of the analyzed CNVs in cases compared with controls.
  
  
  RESULTS
  Recurrent or overlapping CNVs were found in cases at 39.3% of the selected loci. The collective frequency of CNVs at these loci is significantly increased in cases with autism, in cases with schizophrenia, and in cases with mental retardation compared with controls (P < .001, P = .01, and P = .001, respectively, Fisher exact test). Individual significance (P = .02 without correction for multiple testing) was reached for the association between autism and a 350-kilobase deletion located at 22q11 and spanning the PRODH and DGCR6 genes.
  
  
  CONCLUSIONS
  Weakly to moderately recurrent CNVs (transmitted or occurring de novo) seem to be causative or contributory factors for these diseases. Most of these CNVs (which contain genes involved in neurotransmission or in synapse formation and maintenance) are present in the 3 pathologic conditions (schizophrenia, autism, and mental retardation), supporting the existence of shared biologic pathways in these neurodevelopmental disorders.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 614, Institut Hospitalo-Universitaire de Recherche Biomédicale, 76000 Rouen, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Guilmatre
authors.forename: Christèle
authors.initials: C
authors.lastname: Dubourg
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Mosca
authors.forename: Solenn
authors.initials: S
authors.lastname: Legallic
authors.forename: Alice
authors.initials: A
authors.lastname: Goldenberg
authors.forename: Valérie
authors.initials: V
authors.lastname: Drouin-Garraud
authors.forename: Valérie
authors.initials: V
authors.lastname: Layet
authors.forename: Antoine
authors.initials: A
authors.lastname: Rosier
authors.forename: Sylvain
authors.initials: S
authors.lastname: Briault
authors.forename: Frédérique
authors.initials: F
authors.lastname: Bonnet-Brilhault
authors.forename: Frédéric
authors.initials: F
authors.lastname: Laumonnier
authors.forename: Sylvie
authors.initials: S
authors.lastname: Odent
authors.forename: Gael
authors.initials: G
authors.lastname: Le Vacon
authors.forename: Géraldine
authors.initials: G
authors.lastname: Joly-Helas
authors.forename: Véronique
authors.initials: V
authors.lastname: David
authors.forename: Claude
authors.initials: C
authors.lastname: Bendavid
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pinoit
authors.forename: Céline
authors.initials: C
authors.lastname: Henry
authors.forename: Caterina
authors.initials: C
authors.lastname: Impallomeni
authors.forename: Eva
authors.initials: E
authors.lastname: Germano
authors.forename: Gaetano
authors.initials: G
authors.lastname: Tortorella
authors.forename: Gabriella
authors.initials: G
authors.lastname: Di Rosa
authors.forename: Catherine
authors.initials: C
authors.lastname: Barthelemy
authors.forename: Christian
authors.initials: C
authors.lastname: Andres
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Thierry
authors.initials: T
authors.lastname: Frébourg
authors.forename: Pascale
authors.initials: P
authors.lastname: Saugier Veber
authors.forename: Dominique
authors.initials: D
authors.lastname: Campion
mesh_terms: D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D002874:Chromosome Mapping / Q000706:statistics & numerical data; D055028:Comparative Genomic Hybridization / Q000706:statistics & numerical data; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000706:statistics & numerical data; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D055495:Neurogenesis; D020411:Oligonucleotide Array Sequence Analysis; D011392:Proline / Q000097:blood; D011618:Psychotic Disorders / Q000175:diagnosis / Q000235:genetics; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*
chemical_list: D011392:Proline