Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 Sep;66(9):947-56.
doi: 10.1001/archgenpsychiatry.2009.80.

Recurrent rearrangements in synaptic and neurodevelopmental genes and shared biologic pathways in schizophrenia, autism, and mental retardation

Audrey Guilmatre  1 , Christèle Dubourg, Anne-Laure Mosca, Solenn Legallic, Alice Goldenberg, Valérie Drouin-Garraud, Valérie Layet, Antoine Rosier, Sylvain Briault, Frédérique Bonnet-Brilhault, Frédéric Laumonnier, Sylvie Odent, Gael Le Vacon, Géraldine Joly-Helas, Véronique David, Claude Bendavid, Jean-Michel Pinoit, Céline Henry, Caterina Impallomeni, Eva Germano, Gaetano Tortorella, Gabriella Di Rosa, Catherine Barthelemy, Christian Andres, Laurence Faivre, Thierry Frébourg, Pascale Saugier Veber, Dominique Campion
Affiliations
Review

Recurrent rearrangements in synaptic and neurodevelopmental genes and shared biologic pathways in schizophrenia, autism, and mental retardation

Audrey Guilmatre et al. Arch Gen Psychiatry. 2009 Sep.

Abstract

Context: 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.

Objectives: 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.

Design: Case-control study.

Setting: Academic research.

Participants: 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.

Main outcome measures: 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.

PubMed Disclaimer

References

    1. Friedman JM, Baross A, Delaney AD, et al. Oligonucleotide microarray analysis of genomic imbalance in children with mental retardation. Am J Hum Genet. 2006 Sep;79(3):500–513. - PMC - PubMed
    1. Froyen G, Van Esch H, Bauters M, et al. Detection of genomic copy number changes in patients with idiopathic mental retardation by high-resolution X-array-CGH: important role for increased gene dosage of XLMR genes. Hum Mutat. 2007 Oct;28(10):1034–1042. - PubMed
    1. Menten B, Maas N, Thienpont B, et al. Emerging patterns of cryptic chromosomal imbalance in patients with idiopathic mental retardation and multiple congenital anomalies: a new series of 140 patients and review of published reports. J Med Genet. 2006 Aug;43(8):625–633. - PMC - PubMed
    1. Marshall CR, Noor A, Vincent JB, et al. Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet. 2008 Feb;82(2):477–488. - PMC - PubMed
    1. Sebat J, Lakshmi B, Malhotra D, et al. Strong association of de novo copy number mutations with autism. Science. 2007 Apr 20;316(5823):445–449. - PMC - PubMed

MeSH terms