Recurrent Rearrangements in Synaptic and Neurodevelopmental Genes and Shared Biologic Pathways in Schizophrenia, Autism, and Mental Retardation

被引：330

作者：

Guilmatre, Audrey ^{[1
]}

Dubourg, Christele ^{[4
]}

Mosca, Anne-Laure ^{[1
,12
]}

Legallic, Solenn ^{[1
]}

Goldenberg, Alice ^{[3
]}

Drouin-Garraud, Valerie ^{[3
]}

Layet, Valerie ^{[6
]}

Rosier, Antoine ^{[7
]}

Briault, Sylvain ^{[8
,9
]}

Bonnet-Brilhault, Frederique ^{[10
]}

Laumonnier, Frederic ^{[10
]}

Odent, Sylvie ^{[5
]}

Le Vacon, Gael ^{[2
]}

Joly-Helas, Geraldine ^{[3
]}

David, Veronique ^{[4
]}

Bendavid, Claude ^{[4
]}

Pinoit, Jean-Michel ^{[13
]}

Henry, Celine ^{[13
]}

Impallomeni, Caterina ^{[14
]}

Germano, Eva ^{[14
]}

Tortorella, Gaetano ^{[14
]}

Di Rosa, Gabriella ^{[14
]}

Barthelemy, Catherine ^{[10
]}

Andres, Christian ^{[11
]}

Faivre, Laurence ^{[12
]}

Frebourg, Thierry ^{[1
,3
]}

Veber, Pascale Saugier ^{[1
,3
]}

Campion, Dominique ^{[1
,2
]}

机构：

[1] Inst Hosp Univ Rech Biomed, INSERM, U614, F-76000 Rouen, France

[2] Ctr Hosp St Etienne du Rouvray, Dept Res, Rouen, France

[3] Univ Hosp, Dept Genet, Rouen, France

[4] Univ Rennes 1, CNRS, UMR 6061, Rennes, France

[5] Univ Hosp, Dept Genet, Rennes, France

[6] Grp Hosp Havre, Dept Genet, Le Havre, France

[7] Ctr Ressources Autisme Haute Normandie, St Etienne, France

[8] Univ Hosp, Dept Genet, Orleans, France

[9] CNRS, UMR 930, F-45071 Orleans, France

[10] Univ Tours, Univ Hosp Bretonneau, INSERM, U930, Tours, France

[11] INSERM, U619, Tours, France

[12] Univ Hosp, Dept Genet, Dijon, France

[13] Univ Hosp, Childrens Hosp, Ctr Ressources Autisme Bourgogne, Dijon, France

[14] Univ Hosp, Dept Med & Surg Pediat, Messina, Italy

来源：

ARCHIVES OF GENERAL PSYCHIATRY | 2009年 / 66卷 / 09期

关键词：

COPY NUMBER; SPECTRUM DISORDER; ARRAY-CGH; COMMUNICATION DEFICITS; INTERSTITIAL DELETION; DEVELOPMENTAL DELAY; VARIABLE PHENOTYPE; PROXIMAL; 15Q; DUPLICATION; MICRODELETION;

D O I：

10.1001/archgenpsychiatry.2009.80

中图分类号：

R749 [精神病学];

学科分类号：

100205 ;

摘要：

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.

引用

页码：947 / +

页数：15

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