Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia

被引：225

作者：

Piton, A. ^{[1
]}

Gauthier, J. ^{[1
]}

Hamdan, F. F. ^{[2
]}

Lafreniere, R. G. ^{[1
]}

Yang, Y. ^{[1
]}

Henrion, E. ^{[1
]}

Laurent, S. ^{[1
]}

Noreau, A. ^{[1
]}

Thibodeau, P. ^{[1
]}

Karemera, L. ^{[1
]}

Spiegelman, D. ^{[1
]}

Kuku, F. ^{[1
]}

Duguay, J. ^{[1
]}

Destroismaisons, L. ^{[1
]}

Jolivet, P. ^{[1
]}

Cote, M. ^{[1
]}

Lachapelle, K. ^{[1
]}

Diallo, O. ^{[1
]}

Raymond, A. ^{[1
]}

Marineau, C. ^{[1
]}

Champagne, N. ^{[3
,4
]}

Xiong, L. ^{[1
]}

Gaspar, C. ^{[1
]}

Riviere, J-B ^{[1
]}

Tarabeux, J. ^{[1
]}

Cossette, P. ^{[1
]}

Krebs, M-O ^{[5
,6
]}

Rapoport, J. L. ^{[7
]}

Addington, A. ^{[7
]}

DeLisi, L. E. ^{[8
,9
,10
]}

Mottron, L. ^{[11
]}

Joober, R. ^{[12
]}

Fombonne, E. ^{[13
]}

Drapeau, P. ^{[3
,4
]}

Rouleau, G. A. ^{[1
,2
]}

机构：

[1] Univ Montreal, Dept Med, Ctr Excellence Neur, CHUM Res Ctr, Montreal, PQ H2L 4M1, Canada

[2] CHU St Justine Res Ctr, Montreal, PQ, Canada

[3] Univ Montreal, Dept Pathol & Cell Biol, Montreal, PQ H2L 4M1, Canada

[4] Univ Montreal, Grp Rech Syst Nerveux Cent, Montreal, PQ H2L 4M1, Canada

[5] Univ Paris 05, INSERM, U796, F-75252 Paris, France

[6] Ctr Hosp St Anne, Paris, France

[7] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA

[8] VA Boston Healthcare Syst, Brockton, MA USA

[9] Harvard Univ, Sch Med, Brockton, MA 02401 USA

[10] NYU, Dept Psychiat, Langone Med Ctr, New York, NY 10016 USA

[11] CETEDUM, Montreal, PQ, Canada

[12] McGill Univ, Douglas Mental Hlth Univ Inst, Dept Psychiat, Montreal, PQ, Canada

[13] Montreal Childrens Hosp, Dept Psychiat, Montreal, PQ H3H 1P3, Canada

来源：

MOLECULAR PSYCHIATRY | 2011年 / 16卷 / 08期

关键词：

autism spectrum disorder; schizophrenia; X chromosome; synaptic genes; rare variants; LINKED MENTAL-RETARDATION; MONOAMINE-OXIDASE-B; GENOMEWIDE SCREEN; SUSCEPTIBILITY LOCI; LINKAGE DISEQUILIBRIUM; POSTSYNAPTIC DENSITY; ANGELMAN SYNDROME; PROTEIN FAMILY; MUTATIONS; ASSOCIATION;

D O I：

10.1038/mp.2010.54

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Autism spectrum disorder (ASD) and schizophrenia (SCZ) are two common neurodevelopmental syndromes that result from the combined effects of environmental and genetic factors. We set out to test the hypothesis that rare variants in many different genes, including de novo variants, could predispose to these conditions in a fraction of cases. In addition, for both disorders, males are either more significantly or more severely affected than females, which may be explained in part by X-linked genetic factors. Therefore, we directly sequenced 111 X-linked synaptic genes in individuals with ASD (n = 142; 122 males and 20 females) or SCZ (n = 143; 95 males and 48 females). We identified > 200 non-synonymous variants, with an excess of rare damaging variants, which suggest the presence of disease-causing mutations. Truncating mutations in genes encoding the calcium-related protein IL1RAPL1 (already described in Piton et al. Hum Mol Genet 2008) and the monoamine degradation enzyme monoamine oxidase B were found in ASD and SCZ, respectively. Moreover, several promising non-synonymous rare variants were identified in genes encoding proteins involved in regulation of neurite outgrowth and other various synaptic functions (MECP2, TM4SF2/TSPAN7, PPP1R3F, PSMD10, MCF2, SLITRK2, GPRASP2, and OPHN1). Molecular Psychiatry (2011) 16, 867-880; doi:10.1038/mp.2010.54; published online 18 May 2010

引用

页码：867 / 880

页数：14

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