Skip to main content

Advertisement

SpringerLink
Log in

Truncating mutations in NRXN2 and NRXN1 in autism spectrum disorders and schizophrenia

  • Original Investigation
  • Published:
Human Genetics Aims and scope Submit manuscript

Abstract

Growing genetic evidence is converging in favor of common pathogenic mechanisms for autism spectrum disorders (ASD), intellectual disability (ID or mental retardation) and schizophrenia (SCZ), three neurodevelopmental disorders affecting cognition and behavior. Copy number variations and deleterious mutations in synaptic organizing proteins including NRXN1 have been associated with these neurodevelopmental disorders, but no such associations have been reported for NRXN2 or NRXN3. From resequencing the three neurexin genes in individuals affected by ASD (n = 142), SCZ (n = 143) or non-syndromic ID (n = 94), we identified a truncating mutation in NRXN2 in a patient with ASD inherited from a father with severe language delay and family history of SCZ. We also identified a de novo truncating mutation in NRXN1 in a patient with SCZ, and other potential pathogenic ASD mutations. These truncating mutations result in proteins that fail to promote synaptic differentiation in neuron coculture and fail to bind either of the established postsynaptic binding partners LRRTM2 or NLGN2 in cell binding assays. Our findings link NRXN2 disruption to the pathogenesis of ASD for the first time and further strengthen the involvement of NRXN1 in SCZ, supporting the notion of a common genetic mechanism in these disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Belmonte MK, Cook EH Jr, Anderson GM, Rubenstein JL, Greenough WT, Beckel-Mitchener A, Courchesne E, Boulanger LM, Powell SB, Levitt PR, Perry EK, Jiang YH, DeLorey TM, Tierney E (2004) Autism as a disorder of neural information processing: directions for research and targets for therapy. Mol Psychiatry 9:646–663

    PubMed  CAS  Google Scholar 

  • Biederer T, Scheiffele P (2007) Mixed-culture assays for analyzing neuronal synapse formation. Nat Protoc 2:670–676

    Article  PubMed  CAS  Google Scholar 

  • Biederer T, Sudhof TC (2001) CASK and protein 4.1 support F-actin nucleation on neurexins. J Biol Chem 276:47869–47876

    PubMed  CAS  Google Scholar 

  • Boucard AA, Chubykin AA, Comoletti D, Taylor P, Sudhof TC (2005) A splice code for trans-synaptic cell adhesion mediated by binding of neuroligin 1 to alpha- and beta-neurexins. Neuron 48:229–236

    Article  PubMed  CAS  Google Scholar 

  • Braff DL, Geyer MA (1990) Sensorimotor gating and schizophrenia. Human and animal model studies. Arch Gen Psychiatry 47:181–188

    PubMed  CAS  Google Scholar 

  • Ching MS, Shen Y, Tan WH, Jeste SS, Morrow EM, Chen X, Mukaddes NM, Yoo SY, Hanson E, Hundley R, Austin C, Becker RE, Berry GT, Driscoll K, Engle EC, Friedman S, Gusella JF, Hisama FM, Irons MB, Lafiosca T, LeClair E, Miller DT, Neessen M, Picker JD, Rappaport L, Rooney CM, Sarco DP, Stoler JM, Walsh CA, Wolff RR, Zhang T, Nasir RH, Wu BL (2010) Deletions of NRXN1 (neurexin-1) predispose to a wide spectrum of developmental disorders. Am J Med Genet B Neuropsychiatr Genet 153B:937–947

    PubMed  CAS  Google Scholar 

  • Craig AM, Kang Y (2007) Neurexin-neuroligin signaling in synapse development. Curr Opin Neurobiol 17:43–52

    Article  PubMed  CAS  Google Scholar 

  • Craig AM, Graf ER, Linhoff MW (2006) How to build a central synapse: clues from cell culture. Trends Neurosci 29:8–20

    Article  PubMed  CAS  Google Scholar 

  • de Wit J, Sylwestrak E, O’Sullivan ML, Otto S, Tiglio K, Savas JN, Yates JR 3rd, Comoletti D, Taylor P, Ghosh A (2009) LRRTM2 interacts with Neurexin1 and regulates excitatory synapse formation. Neuron 64:799–806

    Article  PubMed  Google Scholar 

  • Dudanova I, Tabuchi K, Rohlmann A, Sudhof TC, Missler M (2007) Deletion of alpha-neurexins does not cause a major impairment of axonal pathfinding or synapse formation. J Comp Neurol 502:261–274

    Article  PubMed  CAS  Google Scholar 

  • Etherton MR, Blaiss CA, Powell CM, Sudhof TC (2009) Mouse neurexin-1alpha deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments. Proc Natl Acad Sci USA 106:17998–18003

    Article  PubMed  CAS  Google Scholar 

  • Feng J, Schroer R, Yan J, Song W, Yang C, Bockholt A, Cook EH Jr, Skinner C, Schwartz CE, Sommer SS (2006) High frequency of neurexin 1beta signal peptide structural variants in patients with autism. Neurosci Lett 409:10–13

    Article  PubMed  CAS  Google Scholar 

  • Francks C, Maegawa S, Lauren J, Abrahams BS, Velayos-Baeza A, Medland SE, Colella S, Groszer M, McAuley EZ, Caffrey TM, Timmusk T, Pruunsild P, Koppel I, Lind PA, Matsumoto-Itaba N, Nicod J, Xiong L, Joober R, Enard W, Krinsky B, Nanba E, Richardson AJ, Riley BP, Martin NG, Strittmatter SM, Moller HJ, Rujescu D, St Clair D, Muglia P, Roos JL, Fisher SE, Wade-Martins R, Rouleau GA, Stein JF, Karayiorgou M, Geschwind DH, Ragoussis J, Kendler KS, Airaksinen MS, Oshimura M, DeLisi LE, Monaco AP (2007) LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia. Mol Psychiatry 12:1129–1139

    Article  PubMed  CAS  Google Scholar 

  • Gauthier J, Champagne N, Lafreniere RG, Xiong L, Spiegelman D, Brustein E, Lapointe M, Peng H, Cote M, Noreau A, Hamdan FF, Addington AM, Rapoport JL, Delisi LE, Krebs MO, Joober R, Fathalli F, Mouaffak F, Haghighi AP, Neri C, Dube MP, Samuels ME, Marineau C, Stone EA, Awadalla P, Barker PA, Carbonetto S, Drapeau P, Rouleau GA (2010) De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia. Proc Natl Acad Sci USA 107:7863–7868

    Article  PubMed  CAS  Google Scholar 

  • Glessner JT, Wang K, Cai G, Korvatska O, Kim CE, Wood S, Zhang H, Estes A, Brune CW, Bradfield JP, Imielinski M, Frackelton EC, Reichert J, Crawford EL, Munson J, Sleiman PM, Chiavacci R, Annaiah K, Thomas K, Hou C, Glaberson W, Flory J, Otieno F, Garris M, Soorya L, Klei L, Piven J, Meyer KJ, Anagnostou E, Sakurai T, Game RM, Rudd DS, Zurawiecki D, McDougle CJ, Davis LK, Miller J, Posey DJ, Michaels S, Kolevzon A, Silverman JM, Bernier R, Levy SE, Schultz RT, Dawson G, Owley T, McMahon WM, Wassink TH, Sweeney JA, Nurnberger JI, Coon H, Sutcliffe JS, Minshew NJ, Grant SF, Bucan M, Cook EH, Buxbaum JD, Devlin B, Schellenberg GD, Hakonarson H (2009) Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature 459:569–573

    Article  PubMed  CAS  Google Scholar 

  • Guilmatre A, Dubourg C, Mosca AL, Legallic S, Goldenberg A, Drouin-Garraud V, Layet V, Rosier A, Briault S, Bonnet-Brilhault F, Laumonnier F, Odent S, Le Vacon G, Joly-Helas G, David V, Bendavid C, Pinoit JM, Henry C, Impallomeni C, Germano E, Tortorella G, Di Rosa G, Barthelemy C, Andres C, Faivre L, Frebourg T, Saugier Veber P, Campion D (2009) Recurrent rearrangements in synaptic and neurodevelopmental genes and shared biologic pathways in schizophrenia, autism, and mental retardation. Arch Gen Psychiatry 66:947–956

    Article  PubMed  CAS  Google Scholar 

  • Hamdan FF, Gauthier J, Spiegelman D, Noreau A, Yang Y, Pellerin S, Dobrzeniecka S, Cote M, Perreault-Linck E, Carmant L, D’Anjou G, Fombonne E, Addington AM, Rapoport JL, Delisi LE, Krebs MO, Mouaffak F, Joober R, Mottron L, Drapeau P, Marineau C, Lafreniere RG, Lacaille JC, Rouleau GA, Michaud JL (2009) Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation. N Engl J Med 360:599–605

    Article  PubMed  CAS  Google Scholar 

  • Harrison PJ (1999) The neuropathology of schizophrenia. A critical review of the data and their interpretation. Brain 122(Pt 4):593–624

    Article  PubMed  Google Scholar 

  • Ichtchenko K, Hata Y, Nguyen T, Ullrich B, Missler M, Moomaw C, Sudhof TC (1995) Neuroligin 1: a splice site-specific ligand for beta-neurexins. Cell 81:435–443

    Article  PubMed  CAS  Google Scholar 

  • Jamain S, Quach H, Betancur C, Rastam M, Colineaux C, Gillberg IC, Soderstrom H, Giros B, Leboyer M, Gillberg C, Bourgeron T (2003) Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet 34:27–29

    Article  PubMed  CAS  Google Scholar 

  • Jamain S, Radyushkin K, Hammerschmidt K, Granon S, Boretius S, Varoqueaux F, Ramanantsoa N, Gallego J, Ronnenberg A, Winter D, Frahm J, Fischer J, Bourgeron T, Ehrenreich H, Brose N (2008) Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism. Proc Natl Acad Sci USA 105:1710–1715

    Article  PubMed  CAS  Google Scholar 

  • Kang Y, Zhang X, Dobie F, Wu H, Craig AM (2008) Induction of GABAergic postsynaptic differentiation by alpha-neurexins. J Biol Chem 283:2323–2334

    Article  PubMed  CAS  Google Scholar 

  • Kim HG, Kishikawa S, Higgins AW, Seong IS, Donovan DJ, Shen Y, Lally E, Weiss LA, Najm J, Kutsche K, Descartes M, Holt L, Braddock S, Troxell R, Kaplan L, Volkmar F, Klin A, Tsatsanis K, Harris DJ, Noens I, Pauls DL, Daly MJ, MacDonald ME, Morton CC, Quade BJ, Gusella JF (2008) Disruption of neurexin 1 associated with autism spectrum disorder. Am J Hum Genet 82:199–207

    Article  PubMed  CAS  Google Scholar 

  • Kirov G, Gumus D, Chen W, Norton N, Georgieva L, Sari M, O’Donovan MC, Erdogan F, Owen MJ, Ropers HH, Ullmann R (2008) Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia. Hum Mol Genet 17:458–465

    Article  PubMed  CAS  Google Scholar 

  • Ko J, Fuccillo MV, Malenka RC, Sudhof TC (2009) LRRTM2 functions as a neurexin ligand in promoting excitatory synapse formation. Neuron 64:791–798

    Article  PubMed  CAS  Google Scholar 

  • Laumonnier F, Bonnet-Brilhault F, Gomot M, Blanc R, David A, Moizard MP, Raynaud M, Ronce N, Lemonnier E, Calvas P, Laudier B, Chelly J, Fryns JP, Ropers HH, Hamel BC, Andres C, Barthelemy C, Moraine C, Briault S (2004) X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. Am J Hum Genet 74:552–557

    Article  PubMed  CAS  Google Scholar 

  • Marshall CR, Noor A, Vincent JB, Lionel AC, Feuk L, Skaug J, Shago M, Moessner R, Pinto D, Ren Y, Thiruvahindrapduram B, Fiebig A, Schreiber S, Friedman J, Ketelaars CE, Vos YJ, Ficicioglu C, Kirkpatrick S, Nicolson R, Sloman L, Summers A, Gibbons CA, Teebi A, Chitayat D, Weksberg R, Thompson A, Vardy C, Crosbie V, Luscombe S, Baatjes R, Zwaigenbaum L, Roberts W, Fernandez B, Szatmari P, Scherer SW (2008) Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet 82:477–488

    Article  PubMed  CAS  Google Scholar 

  • Missler M, Sudhof TC (1998) Neurexins: three genes and 1001 products. Trends Genet 14:20–26

    Article  PubMed  CAS  Google Scholar 

  • Missler M, Zhang W, Rohlmann A, Kattenstroth G, Hammer RE, Gottmann K, Sudhof TC (2003) Alpha-neurexins couple Ca2+ channels to synaptic vesicle exocytosis. Nature 424:939–948

    Article  Google Scholar 

  • Moessner R, Marshall CR, Sutcliffe JS, Skaug J, Pinto D, Vincent J, Zwaigenbaum L, Fernandez B, Roberts W, Szatmari P, Scherer SW (2007) Contribution of SHANK3 mutations to autism spectrum disorder. Am J Hum Genet 81:1289–1297

    Article  PubMed  CAS  Google Scholar 

  • Pinto D, Pagnamenta AT, Klei L, Anney R, Merico D, Regan R, Conroy J, Magalhaes TR, Correia C, Abrahams BS, Almeida J, Bacchelli E, Bader GD, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bolte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Bryson SE, Carson AR, Casallo G, Casey J, Chung BH, Cochrane L, Corsello C, Crawford EL, Crossett A, Cytrynbaum C, Dawson G, de Jonge M, Delorme R, Drmic I, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Fombonne E, Freitag CM, Gilbert J, Gillberg C, Glessner JT, Goldberg J, Green A, Green J, Guter SJ, Hakonarson H, Heron EA, Hill M, Holt R, Howe JL, Hughes G, Hus V, Igliozzi R, Kim C, Klauck SM, Kolevzon A, Korvatska O, Kustanovich V, Lajonchere CM, Lamb JA, Laskawiec M, Leboyer M, Le Couteur A, Leventhal BL, Lionel AC, Liu XQ, Lord C, Lotspeich L, Lund SC, Maestrini E, Mahoney W, Mantoulan C, Marshall CR, McConachie H, McDougle CJ, McGrath J, McMahon WM, Merikangas A, Migita O, Minshew NJ, Mirza GK, Munson J, Nelson SF, Noakes C, Noor A, Nygren G, Oliveira G, Papanikolaou K, Parr JR, Parrini B, Paton T, Pickles A, Pilorge M et al (2010) Functional impact of global rare copy number variation in autism spectrum disorders. Nature 466:368–372

    Article  PubMed  CAS  Google Scholar 

  • Piton A, Gauthier J, Hamdan FF, Lafreniere RG, Yang Y, Henrion E, Laurent S, Noreau A, Thibodeau P, Karemera L, Spiegelman D, Kuku F, Duguay J, Destroismaisons L, Jolivet P, Cote M, Lachapelle K, Diallo O, Raymond A, Marineau C, Champagne N, Xiong L, Gaspar C, Riviere JB, Tarabeux J, Cossette P, Krebs MO, Rapoport JL, Addington A, Delisi LE, Mottron L, Joober R, Fombonne E, Drapeau P, Rouleau GA (2010) Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia. Mol Psychiatry

  • Rujescu D, Ingason A, Cichon S, Pietilainen OP, Barnes MR, Toulopoulou T, Picchioni M, Vassos E, Ettinger U, Bramon E, Murray R, Ruggeri M, Tosato S, Bonetto C, Steinberg S, Sigurdsson E, Sigmundsson T, Petursson H, Gylfason A, Olason PI, Hardarsson G, Jonsdottir GA, Gustafsson O, Fossdal R, Giegling I, Moller HJ, Hartmann AM, Hoffmann P, Crombie C, Fraser G, Walker N, Lonnqvist J, Suvisaari J, Tuulio-Henriksson A, Djurovic S, Melle I, Andreassen OA, Hansen T, Werge T, Kiemeney LA, Franke B, Veltman J, Buizer-Voskamp JE, Sabatti C, Ophoff RA, Rietschel M, Nothen MM, Stefansson K, Peltonen L, St Clair D, Stefansson H, Collier DA (2009) Disruption of the neurexin 1 gene is associated with schizophrenia. Hum Mol Genet 18:988–996

    PubMed  CAS  Google Scholar 

  • Siddiqui TJ, Pancaroglu R, Kang Y, Rooyakkers A, Craig AM (2010) LRRTMs and neuroligins bind neurexins with a differential code to cooperate in glutamate synapse development. J Neurosci 30:7495–7506

    Article  PubMed  CAS  Google Scholar 

  • Sudhof TC (2008) Neuroligins and neurexins link synaptic function to cognitive disease. Nature 455:903–911

    Article  PubMed  Google Scholar 

  • Sugita S, Saito F, Tang J, Satz J, Campbell K, Sudhof TC (2001) A stoichiometric complex of neurexins and dystroglycan in brain. J Cell Biol 154:435–445

    Article  PubMed  CAS  Google Scholar 

  • Swerdlow NR, Braff DL, Taaid N, Geyer MA (1994) Assessing the validity of an animal model of deficient sensorimotor gating in schizophrenic patients. Arch Gen Psychiatry 51:139–154

    PubMed  CAS  Google Scholar 

  • Szatmari P, Paterson AD, Zwaigenbaum L, Roberts W, Brian J, Liu XQ, Vincent JB, Skaug JL, Thompson AP, Senman L, Feuk L, Qian C, Bryson SE, Jones MB, Marshall CR, Scherer SW, Vieland VJ, Bartlett C, Mangin LV, Goedken R, Segre A, Pericak-Vance MA, Cuccaro ML, Gilbert JR, Wright HH, Abramson RK, Betancur C, Bourgeron T, Gillberg C, Leboyer M, Buxbaum JD, Davis KL, Hollander E, Silverman JM, Hallmayer J, Lotspeich L, Sutcliffe JS, Haines JL, Folstein SE, Piven J, Wassink TH, Sheffield V, Geschwind DH, Bucan M, Brown WT, Cantor RM, Constantino JN, Gilliam TC, Herbert M, Lajonchere C, Ledbetter DH, Lese-Martin C, Miller J, Nelson S, Samango-Sprouse CA, Spence S, State M, Tanzi RE, Coon H, Dawson G, Devlin B, Estes A, Flodman P, Klei L, McMahon WM, Minshew N, Munson J, Korvatska E, Rodier PM, Schellenberg GD, Smith M, Spence MA, Stodgell C, Tepper PG, Wijsman EM, Yu CE, Roge B, Mantoulan C, Wittemeyer K, Poustka A, Felder B, Klauck SM, Schuster C, Poustka F, Bolte S, Feineis-Matthews S, Herbrecht E, Schmotzer G, Tsiantis J, Papanikolaou K, Maestrini E, Bacchelli E, Blasi F, Carone S, Toma C, Van Engeland H, de Jonge M, Kemner C, Koop F, Langemeijer M et al (2007) Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat Genet 39:319–328

    Article  PubMed  CAS  Google Scholar 

  • Uemura T, Lee SJ, Yasumura M, Takeuchi T, Yoshida T, Ra M, Taguchi R, Sakimura K, Mishina M (2010) Trans-synaptic interaction of GluRdelta2 and Neurexin through Cbln1 mediates synapse formation in the cerebellum. Cell 141:1068–1079

    Article  PubMed  CAS  Google Scholar 

  • Ushkaryov YA, Petrenko AG, Geppert M, Sudhof TC (1992) Neurexins: synaptic cell surface proteins related to the alpha-latrotoxin receptor and laminin. Science 257:50–56

    Article  PubMed  CAS  Google Scholar 

  • Wilson HL, Wong AC, Shaw SR, Tse WY, Stapleton GA, Phelan MC, Hu S, Marshall J, McDermid HE (2003) Molecular characterisation of the 22q13 deletion syndrome supports the role of haploinsufficiency of SHANK3/PROSAP2 in the major neurological symptoms. J Med Genet 40:575–584

    Article  PubMed  CAS  Google Scholar 

  • Yan J, Noltner K, Feng J, Li W, Schroer R, Skinner C, Zeng W, Schwartz CE, Sommer SS (2008) Neurexin 1alpha structural variants associated with autism. Neurosci Lett 438:368–370

    Article  PubMed  CAS  Google Scholar 

  • Zahir FR, Baross A, Delaney AD, Eydoux P, Fernandes ND, Pugh T, Marra MA, Friedman JM (2008) A patient with vertebral, cognitive and behavioural abnormalities and a de novo deletion of NRXN1alpha. J Med Genet 45:239–243

    Article  PubMed  CAS  Google Scholar 

  • Zhang C, Milunsky JM, Newton S, Ko J, Zhao G, Maher TA, Tager-Flusberg H, Bolliger MF, Carter AS, Boucard AA, Powell CM, Sudhof TC (2009) A neuroligin-4 missense mutation associated with autism impairs neuroligin-4 folding and endoplasmic reticulum export. J Neurosci 29:10843–10854

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank all families who kindly participated in this study. We are also thankful to all other S2D members. This work was supported by Genome Canada and Génome Québec, GRSNC of the Fonds de Recherche en Santé du Québec, and received co-funding from Université de Montréal for the ‘Synapse to Disease’ (S2D) project as well as funding from the Canadian Foundation for Innovation. The NSID cohort was recruited with funding from the Réseau de Médecine Génétique Appliquée (RMGA). Functional analysis was supported by Canadian Institutes of Health Research grant MOP84241 and National Institutes of Health grant MH70860 (to A.M.C.). G.A.R. holds the Canada Research Chair in Genetics of the Nervous System; A.M.C. holds the Canada Research Chair in Neurobiology; P.D. holds the Canada Research Chair in Neuroscience; T.J.S. holds a Michael Smith Foundation for Health Research Postdoctoral Fellowship. A portion of the Schizophrenia cohort was collected through the Collaborative Network for Family Study in Psychiatry (“Réseau d’étude familiale en Psychiatry”, REFAPSY), supported by the Fondation Pierre Deniker. We also acknowledge the efforts of the members and Génome Québec Innovation Centre Sequencing (Pierre Lepage, Sébastien Brunet and Hao Fan Yam) and Bioinformatic (Louis Létourneau and Louis Dumond Joseph) groups, and thank Xiling Zhou for preparation of neuron cultures.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Centre of Excellence in Neuromics of Université de Montréal, Centre Hospitalier de l’Université de Montréal, Montreal, Canada

    Julie Gauthier, Dan Spiegelman, Anne Noreau, Ronald G. Lafrenière & Guy A. Rouleau

  2. Department of Medicine, Université of Montréal, Montreal, Canada

    Julie Gauthier, Dan Spiegelman, Anne Noreau, Ronald G. Lafrenière & Guy A. Rouleau

  3. Department of Psychiatry, Brain Research Centre, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada

    Tabrez J. Siddiqui, Daisaku Yokomaku & Ann Marie Craig

  4. McGill University Department of Neurology, Centre for Research in Neuroscience, Montreal General Hospital, McGill University Health Centre, 1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada

    Peng Huashan & Salvatore Carbonetto

  5. Centre of Excellence in Neuromics of Université de Montréal, CHU Sainte-Justine Research Center, 3175, Côte Ste-Catherine, 6th Floor, Block 7, Montreal, QC, H3T 1C5, Canada

    Fadi F. Hamdan & Jacques L. Michaud

  6. Department of Pathology and Cell Biology, Le Groupe de Recherche sur le Système Nerveux Central, Université de Montréal, Montreal, Canada

    Nathalie Champagne, Mathieu Lapointe & Pierre Drapeau

  7. Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Pavilion Frank B. Common Rm. F-2142, 6875 LaSalle Blvd, Verdun, Montreal, QC, H4H 1R3, Canada

    Ferid Fathalli & Ridha Joober

  8. Laboratory of Pathophysiology of Psychiatric Diseases, University Paris Descartes, U894, Sainte-Anne Hospital, 7 rue Cabanis, 75014, Paris, France

    Marie-Odile Krebs

  9. VA Boston Healthcare Service, Harvard Medical School, Brockton, MA, USA

    Lynn E. DeLisi

  10. Pervasive Developmental Disorders Specialized Clinic, Rivière-des-Prairies Hospital, University of Montreal, Montreal, QC, H1E 1A4, Canada

    Laurent Mottron

  11. Department of Psychiatry, Montreal Children’s Hospital, Montreal, QC, H3Z 1P2, Canada

    Éric Fombonne

  12. CHUM Research Centre, 2099, Alexandre De-Seve Street, Room Y-3633, Montreal, QC, H2L 2W5, Canada

    Guy A. Rouleau

Authors
  1. Julie Gauthier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tabrez J. Siddiqui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peng Huashan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daisaku Yokomaku
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fadi F. Hamdan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nathalie Champagne
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mathieu Lapointe
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Dan Spiegelman
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Anne Noreau
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ronald G. Lafrenière
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ferid Fathalli
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ridha Joober
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Marie-Odile Krebs
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Lynn E. DeLisi
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Laurent Mottron
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Éric Fombonne
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Jacques L. Michaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Pierre Drapeau
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Salvatore Carbonetto
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Ann Marie Craig
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Guy A. Rouleau
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ann Marie Craig or Guy A. Rouleau.

Additional information

J. Gauthier, T. J. Siddiqui contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 13883 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gauthier, J., Siddiqui, T.J., Huashan, P. et al. Truncating mutations in NRXN2 and NRXN1 in autism spectrum disorders and schizophrenia. Hum Genet 130, 563–573 (2011). https://doi.org/10.1007/s00439-011-0975-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00439-011-0975-z

Keywords

Search

Navigation