De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia

被引：299

作者：

Gauthier, Julie ^{[1
,2
]}

Champagne, Nathalie ^{[3
,4
]}

Lafreniere, Ronald G. ^{[1
,2
]}

Xiong, Lan ^{[1
,2
]}

Spiegelman, Dan ^{[1
,2
]}

Brustein, Edna ^{[3
,4
]}

Lapointe, Mathieu ^{[3
,4
]}

Peng, Huashan ^{[3
,4
]}

Cote, Melanie ^{[1
,2
]}

Noreau, Anne ^{[1
,2
]}

Hamdan, Fadi F. ^{[5
]}

Addington, Anjene M. ^{[6
]}

Rapoport, Judith L. ^{[6
]}

DeLisi, Lynn E. ^{[7
]}

Krebs, Marie-Odile ^{[8
]}

Joober, Ridha ^{[9
]}

Fathalli, Ferid ^{[9
]}

Mouaffak, Faycal ^{[8
]}

Haghighi, Ali P. ^{[10
]}

Neri, Christian ^{[11
]}

Dube, Marie-Pierre ^{[12
,13
]}

Samuels, Mark E. ^{[5
]}

Marineau, Claude ^{[1
,2
]}

Stone, Eric A. ^{[14
]}

Awadalla, Philip ^{[15
,16
]}

Barker, Philip A. ^{[17
]}

Carbonetto, Salvatore ^{[10
,18
]}

Drapeau, Pierre ^{[3
,4
]}

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

机构：

[1] Univ Montreal, CHU Montreal, Res Ctr, Ctr Excellence Neurom, Montreal, PQ H2L 2W5, Canada

[2] Univ Montreal, Dept Med, Montreal, PQ H2L 2W5, Canada

[3] Univ Montreal, Dept Pathol & Cell Biol, Montreal, PQ H3T 1J4, Canada

[4] Univ Montreal, Grp Rech Syst Nerveux Cent, Montreal, PQ H3T 1J4, Canada

[5] Univ Montreal, Ctr Excellence Neurom, CHU St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada

[6] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA

[7] Harvard Univ, Sch Med, Vet Adm Boston Healthcare Syst, Brockton, MA 02301 USA

[8] Univ Paris 05, Lab Pathophysiol Psychiat Dis, U894, Hop St Anne, F-75014 Paris, France

[9] McGill Univ, Dept Psychiat, Douglas Mental Hlth Univ Inst, Montreal, PQ H4H 1R3, Canada

[10] McGill Univ, Dept Physiol, Montreal, PQ H3G 0B1, Canada

[11] Ctr Paul Broca, INSERM, U857, F-75014 Paris, France

[12] Univ Montreal, Ctr Rech, Inst Cardiol Montreal, Montreal, PQ H1T 1C8, Canada

[13] Univ Montreal, Dept Pharmacol, Montreal, PQ H1T 1C8, Canada

[14] N Carolina State Univ, Raleigh, NC 27695 USA

[15] Univ Montreal, Res Ctr, CHU St Justine, Montreal, PQ H3T 1C5, Canada

[16] Univ Montreal, Dept Pediat & Biochem, Montreal, PQ H3T 1C5, Canada

[17] McGill Univ, Montreal Neurol Inst, Ctr Neuronal Survival, Montreal, PQ H3A 2B4, Canada

[18] McGill Univ, Ctr Res Neurosci, Ctr Hlth, Montreal Gen Hosp, Montreal, PQ H3G 1A4, Canada

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 17期

关键词：

CHROMOSOME; 22Q; BIPOLAR DISORDER; PREMORBID IQ; LINKAGE; EXPRESSION; GENOME; TRANSMISSION; ZEBRAFISH; ALLELES; LOCUS;

D O I：

10.1073/pnas.0906232107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Schizophrenia likely results from poorly understood genetic and environmental factors. We studied the gene encoding the synaptic protein SHANK3 in 285 controls and 185 schizophrenia patients with unaffected parents. Two de novo mutations (R1117X and R536W) were identified in two families, one being found in three affected brothers, suggesting germline mosaicism. Zebrafish and rat hippocampal neuron assays revealed behavior and differentiation defects resulting from the R1117X mutant. As mutations in SHANK3 were previously reported in autism, the occurrence of SHANK3 mutations in subjects with a schizophrenia phenotype suggests a molecular genetic link between these two neurodevelopmental disorders.

引用

页码：7863 / 7868

页数：6

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