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

Julie Gauthier; Nathalie Champagne; Ronald G. Lafrenière; Lan Xiong; Dan Spiegelman; Edna Brustein; Mathieu Lapointe; Huashan Peng; Mélanie Côté; Anne Noreau; Fadi F. Hamdan; Anjené M. Addington; Judith L. Rapoport; Lynn E. DeLisi; Marie Odile Krebs; Ridha Joober; Ferid Fathalli; Fayçal Mouaffak; Ali P. Haghighi; Christian Néri; Marie Pierre Dubé; Mark E. Samuels; Claude Marineau; Eric A. Stone; Philip Awadalla; Philip A. Barker; Salvatore Carbonetto; Pierre Drapeau; Guy A. Rouleau; Kathleen Daignault; Ousmane Diallo; Joannie Duguay; Marina Drits; Edouard Henrion; Philippe Jolivet; Frédéric Kuku; Karine Lachapelle; Guy Laliberté; Sandra Laurent; Meijiang Liao; Carlos Marino; Amélie Piton; Annie Raymond; Annie Reynolds; Daniel Rochefort; Judith St-Onge; Pascale Thibodeau; Kazuya Tsurudome; Yan Yang; Sophie Leroy; Katia Ossian; Mélanie Chayet; David Gourion

doi:10.1073/pnas.0906232107

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

Julie Gauthier^*, Nathalie Champagne, Ronald G. Lafrenière, Lan Xiong, Dan Spiegelman, Edna Brustein, Mathieu Lapointe, Huashan Peng, Mélanie Côté, Anne Noreau, Fadi F. Hamdan, Anjené M. Addington, Judith L. Rapoport, Lynn E. DeLisi, Marie Odile Krebs, Ridha Joober, Ferid Fathalli, Fayçal Mouaffak, Ali P. Haghighi, Christian NériMarie Pierre Dubé, Mark E. Samuels, Claude Marineau, Eric A. Stone, Philip Awadalla, Philip A. Barker, Salvatore Carbonetto, Pierre Drapeau, Guy A. Rouleau, Kathleen Daignault, Ousmane Diallo, Joannie Duguay, Marina Drits, Edouard Henrion, Philippe Jolivet, Frédéric Kuku, Karine Lachapelle, Guy Laliberté, Sandra Laurent, Meijiang Liao, Carlos Marino, Amélie Piton, Annie Raymond, Annie Reynolds, Daniel Rochefort, Judith St-Onge, Pascale Thibodeau, Kazuya Tsurudome, Yan Yang, Sophie Leroy, Katia Ossian, Mélanie Chayet, David Gourion

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English
Pages (from-to)	7863-7868
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	107
Issue number	17
DOIs	https://doi.org/10.1073/pnas.0906232107
Publication status	Published - 27 Apr 2010
Externally published	Yes

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10.1073/pnas.0906232107

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Gauthier, J., Champagne, N., Lafrenière, R. G., Xiong, L., Spiegelman, D., Brustein, E., Lapointe, M., Peng, H., Côté, M., Noreau, A., Hamdan, F. F., Addington, A. M., Rapoport, J. L., DeLisi, L. E., Krebs, M. O., Joober, R., Fathalli, F., Mouaffak, F., Haghighi, A. P., ... Gourion, D. (2010). De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia. Proceedings of the National Academy of Sciences of the United States of America, 107(17), 7863-7868. https://doi.org/10.1073/pnas.0906232107

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abstract = "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.",

author = "Julie Gauthier and Nathalie Champagne and Lafreni{\`e}re, {Ronald G.} and Lan Xiong and Dan Spiegelman and Edna Brustein and Mathieu Lapointe and Huashan Peng and M{\'e}lanie C{\^o}t{\'e} and Anne Noreau and Hamdan, {Fadi F.} and Addington, {Anjen{\'e} M.} and Rapoport, {Judith L.} and DeLisi, {Lynn E.} and Krebs, {Marie Odile} and Ridha Joober and Ferid Fathalli and Fay{\c c}al Mouaffak and Haghighi, {Ali P.} and Christian N{\'e}ri and Dub{\'e}, {Marie Pierre} and Samuels, {Mark E.} and Claude Marineau and Stone, {Eric A.} and Philip Awadalla and Barker, {Philip A.} and Salvatore Carbonetto and Pierre Drapeau and Rouleau, {Guy A.} and Kathleen Daignault and Ousmane Diallo and Joannie Duguay and Marina Drits and Edouard Henrion and Philippe Jolivet and Fr{\'e}d{\'e}ric Kuku and Karine Lachapelle and Guy Lalibert{\'e} and Sandra Laurent and Meijiang Liao and Carlos Marino and Am{\'e}lie Piton and Annie Raymond and Annie Reynolds and Daniel Rochefort and Judith St-Onge and Pascale Thibodeau and Kazuya Tsurudome and Yan Yang and Sophie Leroy and Katia Ossian and M{\'e}lanie Chayet and David Gourion",

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Gauthier, J, Champagne, N, Lafrenière, RG, Xiong, L, Spiegelman, D, Brustein, E, Lapointe, M, Peng, H, Côté, M, Noreau, A, Hamdan, FF, Addington, AM, Rapoport, JL, DeLisi, LE, Krebs, MO, Joober, R, Fathalli, F, Mouaffak, F, Haghighi, AP, Néri, C, Dubé, MP, Samuels, ME, Marineau, C, Stone, EA, Awadalla, P, Barker, PA, Carbonetto, S, Drapeau, P, Rouleau, GA, Daignault, K, Diallo, O, Duguay, J, Drits, M, Henrion, E, Jolivet, P, Kuku, F, Lachapelle, K, Laliberté, G, Laurent, S, Liao, M, Marino, C, Piton, A, Raymond, A, Reynolds, A, Rochefort, D, St-Onge, J, Thibodeau, P, Tsurudome, K, Yang, Y, Leroy, S, Ossian, K, Chayet, M & Gourion, D 2010, 'De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia', Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 17, pp. 7863-7868. https://doi.org/10.1073/pnas.0906232107

De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia. / Gauthier, Julie; Champagne, Nathalie; Lafrenière, Ronald G. et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 17, 27.04.2010, p. 7863-7868.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia

AU - Gauthier, Julie

AU - Champagne, Nathalie

AU - Lafrenière, Ronald G.

AU - Xiong, Lan

AU - Spiegelman, Dan

AU - Brustein, Edna

AU - Lapointe, Mathieu

AU - Peng, Huashan

AU - Côté, Mélanie

AU - Noreau, Anne

AU - Hamdan, Fadi F.

AU - Addington, Anjené M.

AU - Rapoport, Judith L.

AU - DeLisi, Lynn E.

AU - Krebs, Marie Odile

AU - Joober, Ridha

AU - Fathalli, Ferid

AU - Mouaffak, Fayçal

AU - Haghighi, Ali P.

AU - Néri, Christian

AU - Dubé, Marie Pierre

AU - Samuels, Mark E.

AU - Marineau, Claude

AU - Stone, Eric A.

AU - Awadalla, Philip

AU - Barker, Philip A.

AU - Carbonetto, Salvatore

AU - Drapeau, Pierre

AU - Rouleau, Guy A.

AU - Daignault, Kathleen

AU - Diallo, Ousmane

AU - Duguay, Joannie

AU - Drits, Marina

AU - Henrion, Edouard

AU - Jolivet, Philippe

AU - Kuku, Frédéric

AU - Lachapelle, Karine

AU - Laliberté, Guy

AU - Laurent, Sandra

AU - Liao, Meijiang

AU - Marino, Carlos

AU - Piton, Amélie

AU - Raymond, Annie

AU - Reynolds, Annie

AU - Rochefort, Daniel

AU - St-Onge, Judith

AU - Thibodeau, Pascale

AU - Tsurudome, Kazuya

AU - Yang, Yan

AU - Leroy, Sophie

AU - Ossian, Katia

AU - Chayet, Mélanie

AU - Gourion, David

PY - 2010/4/27

Y1 - 2010/4/27

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77952374703&partnerID=8YFLogxK

U2 - 10.1073/pnas.0906232107

DO - 10.1073/pnas.0906232107

M3 - Article

SN - 0027-8424

VL - 107

SP - 7863

EP - 7868

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 17

ER -

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

Abstract

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