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.
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.
Authors: George Zogopoulos; Kevin C H Ha; Faisal Naqib; Sara Moore; Hyeja Kim; Alexandre Montpetit; Frederick Robidoux; Philippe Laflamme; Michelle Cotterchio; Celia Greenwood; Stephen W Scherer; Brent Zanke; Thomas J Hudson; Gary D Bader; Steven Gallinger Journal: Hum Genet Date: 2007-07-19 Impact factor: 4.132
Authors: Christian R Marshall; Abdul Noor; John B Vincent; Anath C Lionel; Lars Feuk; Jennifer Skaug; Mary Shago; Rainald Moessner; Dalila Pinto; Yan Ren; Bhooma Thiruvahindrapduram; Andreas Fiebig; Stefan Schreiber; Jan Friedman; Cees E J Ketelaars; Yvonne J Vos; Can Ficicioglu; Susan Kirkpatrick; Rob Nicolson; Leon Sloman; Anne Summers; Clare A Gibbons; Ahmad Teebi; David Chitayat; Rosanna Weksberg; Ann Thompson; Cathy Vardy; Vicki Crosbie; Sandra Luscombe; Rebecca Baatjes; Lonnie Zwaigenbaum; Wendy Roberts; Bridget Fernandez; Peter Szatmari; Stephen W Scherer Journal: Am J Hum Genet Date: 2008-01-17 Impact factor: 11.025
Authors: Rainald Moessner; Christian R Marshall; James S Sutcliffe; Jennifer Skaug; Dalila Pinto; John Vincent; Lonnie Zwaigenbaum; Bridget Fernandez; Wendy Roberts; Peter Szatmari; Stephen W Scherer Journal: Am J Hum Genet Date: 2007-10-16 Impact factor: 11.025
Authors: Ravinesh A Kumar; Samer KaraMohamed; Jyotsna Sudi; Donald F Conrad; Camille Brune; Judith A Badner; T Conrad Gilliam; Norma J Nowak; Edwin H Cook; William B Dobyns; Susan L Christian Journal: Hum Mol Genet Date: 2007-12-21 Impact factor: 6.150
Authors: Hyung-Goo Kim; Shotaro Kishikawa; Anne W Higgins; Ihn-Sik Seong; Diana J Donovan; Yiping Shen; Eric Lally; Lauren A Weiss; Juliane Najm; Kerstin Kutsche; Maria Descartes; Lynn Holt; Stephen Braddock; Robin Troxell; Lee Kaplan; Fred Volkmar; Ami Klin; Katherine Tsatsanis; David J Harris; Ilse Noens; David L Pauls; Mark J Daly; Marcy E MacDonald; Cynthia C Morton; Bradley J Quade; James F Gusella Journal: Am J Hum Genet Date: 2008-01 Impact factor: 11.025
Authors: Lauren A Weiss; Yiping Shen; Joshua M Korn; Dan E Arking; David T Miller; Ragnheidur Fossdal; Evald Saemundsen; Hreinn Stefansson; Manuel A R Ferreira; Todd Green; Orah S Platt; Douglas M Ruderfer; Christopher A Walsh; David Altshuler; Aravinda Chakravarti; Rudolph E Tanzi; Kari Stefansson; Susan L Santangelo; James F Gusella; Pamela Sklar; Bai-Lin Wu; Mark J Daly Journal: N Engl J Med Date: 2008-01-09 Impact factor: 91.245
Authors: Rachel M Jones; Gemma Cadby; John Blangero; Lawrence J Abraham; Andrew J O Whitehouse; Eric K Moses Journal: Psychiatr Genet Date: 2014-12 Impact factor: 2.458
Authors: Thomas V Fernandez; Stephan J Sanders; Ilana R Yurkiewicz; A Gulhan Ercan-Sencicek; Young-Shin Kim; Daniel O Fishman; Melanie J Raubeson; Youeun Song; Katsuhito Yasuno; Winson S C Ho; Kaya Bilguvar; Joseph Glessner; Su Hee Chu; James F Leckman; Robert A King; Donald L Gilbert; Gary A Heiman; Jay A Tischfield; Pieter J Hoekstra; Bernie Devlin; Hakon Hakonarson; Shrikant M Mane; Murat Günel; Matthew W State Journal: Biol Psychiatry Date: 2011-12-14 Impact factor: 13.382
Authors: C Toma; B Torrico; A Hervás; R Valdés-Mas; A Tristán-Noguero; V Padillo; M Maristany; M Salgado; C Arenas; X S Puente; M Bayés; B Cormand Journal: Mol Psychiatry Date: 2013-09-03 Impact factor: 15.992
Authors: Shashwath A Meda; Gualberto Ruaño; Andreas Windemuth; Kasey O'Neil; Clifton Berwise; Sabra M Dunn; Leah E Boccaccio; Balaji Narayanan; Mohan Kocherla; Emma Sprooten; Matcheri S Keshavan; Carol A Tamminga; John A Sweeney; Brett A Clementz; Vince D Calhoun; Godfrey D Pearlson Journal: Proc Natl Acad Sci U S A Date: 2014-04-28 Impact factor: 11.205
Authors: Elina Jokiranta; Andre Sourander; Auli Suominen; Laura Timonen-Soivio; Alan S Brown; Matti Sillanpää Journal: J Autism Dev Disord Date: 2014-10