The complex genetics in autism spectrum disorders
详细信息    查看全文 | 推荐本文 |
  • 英文篇名:The complex genetics in autism spectrum disorders
  • 作者:HUA ; Rui ; WEI ; MengPing ; ZHANG ; Chen
  • 英文作者:HUA Rui;WEI MengPing;ZHANG Chen;State Key Laboratory of Membrane Biology, School of Life Sciences;PKU-IDG/Mc Govern Institute for Brain Research, Peking University;
  • 英文关键词:autism spectrum disorders,genetics,causative genes,copy number variants
  • 中文刊名:JCXG
  • 英文刊名:中国科学:生命科学(英文版)
  • 机构:State Key Laboratory of Membrane Biology, School of Life Sciences;PKU-IDG/Mc Govern Institute for Brain Research, Peking University;
  • 出版日期:2015-10-05
  • 出版单位:Science China(Life Sciences)
  • 年:2015
  • 期:v.58
  • 基金:supported by National Basic Research Program of China(2011CB809102,2014CB942804,2014BAI03B01,2012YQ0302604);; National Natural Science Foundation of China(31222025,31171025);; Program for New Century Excellent Talents in University of Ministry of Education of China(ZC);; the Project Sponsored by the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry(ZC)
  • 语种:英文;
  • 页:JCXG201510002
  • 页数:13
  • CN:10
  • ISSN:11-5841/Q
  • 分类号:9-21
摘要
Autism spectrum disorders(ASD) are a pervasive neurodevelopmental disease characterized by deficits in social interaction and nonverbal communication, as well as restricted interests and stereotypical behavior. Genetic changes/heritability is one of the major contributing factors, and hundreds to thousands of causative and susceptible genes, copy number variants(CNVs), linkage regions, and micro RNAs have been associated with ASD which clearly indicates that ASD is a complex genetic disorder. Here, we will briefly summarize some of the high-confidence genetic changes in ASD and their possible roles in their pathogenesis.
        Autism spectrum disorders(ASD) are a pervasive neurodevelopmental disease characterized by deficits in social interaction and nonverbal communication, as well as restricted interests and stereotypical behavior. Genetic changes/heritability is one of the major contributing factors, and hundreds to thousands of causative and susceptible genes, copy number variants(CNVs), linkage regions, and micro RNAs have been associated with ASD which clearly indicates that ASD is a complex genetic disorder. Here, we will briefly summarize some of the high-confidence genetic changes in ASD and their possible roles in their pathogenesis.
引文
1 Szatmari P,Jones MB,Zwaigenbaum L,Mac Lean JE.Genetics of autism:overview and new directions.J Autism Dev Disord,1998,28:351 –368
    2 Xu LM,Li JR,Huang Y,Zhao M,Tang X,Wei L.Autismkb:an evidence-based knowledgebase of autism genetics.Nucleic Acids Res,2012,40:D1016–D1022
    3 Hallmayer J,Cleveland S,Torres A,Phillips J,Cohen B,Torigoe T,Miller J,Fedele A,Collins J,Smith K,Lotspeich L,Croen LA,Ozonoff S,Lajonchere C,Grether JK,Risch N.Genetic heritability and shared environmental factors among twin pairs with autism.Arch Gen Psychiatry,2011,68:1095–1102
    4 Bolton P,Macdonald H,Pickles A,Rios P,Goode S,Crowson M,Bailey A,Rutter M.A case-control family history study of autism.J Child Psychol Psychiatry,1994,35:877–900
    5 Ritvo ER,Jorde LB,Mason-Brothers A,Freeman BJ,Pingree C,Jones MB,Mc Mahon WM,Petersen PB,Jenson WR,Mo A.The UCLA-university of Utah epidemiologic survey of autism:recurrence risk estimates and genetic counseling.Am J Psychiatry,1989,146:1032–1036
    6 Spiker D,Lotspeich L,Kraemer HC,Hallmayer J,Mc Mahon W,Petersen PB,Nicholas P,Pingree C,Wiese-Slater S,Chiotti C,Wong DL,Dimicelli S,Ritvo E,Cavalli-Sforza LL,Ciaranello RD.Genetics of autism:characteristics of affected and unaffected children from 37 multiplex families.Am J Med Genet,1994,54:27–35
    7 Folstein S,Rutter M.Infantile autism:a genetic study of 21 twin pairs.J Child Psychol Psychiatry,1977,18:297–321
    8 Ritvo ER,Freeman BJ,Mason-Brothers A,Mo A,Ritvo AM.Concordance for the syndrome of autism in 40 pairs of afflicted twins.Am J Psychiatry,1985,142:74–77
    9 Steffenburg S,Gillberg C,Hellgren L,Andersson L,Gillberg IC,Jakobsson G,Bohman M.A twin study of autism in denmark,finland,iceland,norway and sweden.J Child Psychol Psychiatry,1989,30:405 –416
    10 Bailey A,Le Couteur A,Gottesman I,Bolton P,Simonoff E,YuzdaE,Rutter M.Autism as a strongly genetic disorder:evidence from a british twin study.Psychol Med,1995,25:63–77
    11 Pickles A,Bolton P,Macdonald H,Bailey A,Le Couteur A,Sim CH,Rutter M.Latent-class analysis of recurrence risks for complex phenotypes with selection and measurement error:a twin and family history study of autism.Am J Hum Genet,1995,57:717–726
    12 Greenberg DA,Hodge SE,Sowinski J,Nicoll D.Excess of twins among affected sibling pairs with autism:implications for the etiology of autism.Am J Hum Genet,2001,69:1062–1067
    13 Provenzano G,Zunino G,Genovesi S,SgadóP,Bozzi Y.Mutant mouse models of autism spectrum disorders.Dis Markers,2012,33:225 –239
    14 Moy SS,Nadler JJ,Magnuson TR,Crawley JN.Mouse models of autism spectrum disorders:the challenge for behavioral genetics.Am J Med Genet C Semin Med Genet,2006,142C:40–51
    15 Vorstman JA,Staal WG,van Daalen E,van Engeland H,Hochstenbach PF,Franke L.Identification of novel autism candidate regions through analysis of reported cytogenetic abnormalities associated with autism.Mol Psychiatry,2006,11:1,18–28
    16 Beaudet AL.Autism:highly heritable but not inherited.Nat Med,2007,13:534–536
    17 Jacquemont ML,Sanlaville D,Redon R,Raoul O,Cormier-Daire V,Lyonnet S,Amiel J,Le Merrer M,Heron D,de Blois MC,Prieur M,Vekemans M,Carter NP,Munnich A,Colleaux L,Philippe A.Array-based comparative genomic hybridisation identifies high frequency of cryptic chromosomal rearrangements in patients with syndromic autism spectrum disorders.J Med Genet,2006,43:843 –849
    18 Sebat J,Lakshmi B,Malhotra D,Troge J,Lese-Martin C,Walsh T,Yamrom B,Yoon S,Krasnitz A,Kendall J,Leotta A,Pai D,Zhang R,Lee YH,Hicks J,Spence SJ,Lee AT,Puura K,Lehtim?ki T,Ledbetter D,Gregersen PK,Bregman J,Sutcliffe JS,Jobanputra V,Chung W,Warburton D,King MC,Skuse D,Geschwind DH,Gilliam TC,Ye K,Wigler M.Strong association of de novo copy number mutations with autism.Science,2007,316:445–449
    19 Gilman SR,Iossifov I,Levy D,Ronemus M,Wigler M,Vitkup D.Rare de novo variants associated with autism implicate a large functional network of genes involved in formation and function of synapses.Neuron,2011,70:898–907
    20 Simon EW,Haas-Givler B,Finucane B.A longitudinal follow-up study of autistic symptoms in children and adults with duplications of15 q11-13.Am J Med Genet B Neuropsychiatr Genet,2010,153B:463 –467
    21 Bremer A,Giacobini M,Nordenskjold M,Br?ndum-Nielsen K,Mansouri M,Dahl N,Anderlid B,Schoumans J.Screening for copy number alterations in loci associated with autism spectrum disorders by two-color multiplex ligation-dependent probe amplification.Am J Med Genet B Neuropsychiatr Genet,2010,153B:280–285
    22 Kwasnicka-Crawford DA,Roberts W,Scherer SW.Characterization of an autism-associated segmental maternal heterodisomy of the chromosome 15q11-13 region.J Autism Dev Disord,2007,37:694 –702
    23 Koochek M,Harvard C,Hildebrand MJ,Van Allen M,Wingert H,Mickelson E,Holden JJ,Rajcan-Separovic E,Lewis ME.15q duplication associated with autism in a multiplex family with a familial cryptic translocation t(14;15)(q11.2;q13.3)detected using array-CGH.Clin Genet,2006,69:124–134
    24 Bolton PF,Veltman MW,Weisblatt E,Holmes JR,Thomas NS,Youings SA,Thompson RJ,Roberts SE,Dennis NR,Browne CE,Goodson S,Moore V,Brown J.Chromosome 15q11-13abnormalities and other medical conditions in individuals with autism spectrum disorders.Psychiatr Genet,2004,14:131–137
    25 Bundey S,Hardy C,Vickers S,Kilpatrick MW,Corbett JA.Duplication of the 15q11-13 region in a patient with autism,epilepsy and ataxia.Dev Med Child Neurol,1994,36:736–742
    26 Baker P,Piven J,Schwartz S,Patil S.Brief report:duplication of chromosome 15q11-13 in two individuals with autistic disorder.J Autism Dev Disord,1994,24:529–535
    27 Emanuel BS,Shaikh TH.Segmental duplications:An“expanding”role in genomic instability and disease.Nat Rev Genet,2001,2:791 –800
    28 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,De Lorey TM,Tierney E.Autism as a disorder of neural information processing:directions for research and targets for therapy.Mol Psychiatry,2004,9:646–663
    29 Cook EH Jr,Scherer SW.Copy-number variations associated with neuropsychiatric conditions.Nature,2008,455:919–923
    30 Dykens EM,Sutcliffe JS,Levitt P.Autism and 15q11-q13 disorders:behavioral,genetic,and pathophysiological issues.Ment Retard Dev Disabil Res Rev,2004,10:284–291
    31 Folstein SE,Rosen-Sheidley B.Genetics of autism:complex aetiology for a heterogeneous disorder.Nat Rev Genet,2001,2:943 –955
    32 Lord C,Cook EH,Leventhal BL,Amaral DG.Autism spectrum disorders.Neuron,2000,28:355–363
    33 Maestrini E,Paul A,Monaco AP,Bailey A.Identifying autism susceptibility genes.Neuron,2000,28:19–24
    34 Veenstra-Vanderweele J,Christian SL,Cook EH Jr.Autism as a paradigmatic complex genetic disorder.Annu Rev Genomics Hum Genet,2004,5:379–405
    35 Veenstra-Vander Weele J,Cook EH Jr.Molecular genetics of autism spectrum disorder.Mol Psychiatry,2004,9:819–832
    36 Nicholls RD,Knepper JL.Genome organization,function,and imprinting in Prader-Willi and Angelman syndromes.Annu Rev Genomics Hum Genet,2001,2:153–175
    37 Valente KD,Varela MC,Koiffmann CP,Andrade JQ,Grossmann R,Kok F,Marques-Dias MJ.Angelman syndrome caused by deletion:a genotype-phenotype correlation determined by breakpoint.Epilepsy Res,2013,105:234–239
    38 Kuwano A,Mutirangura A,Dittrich B,Buiting K,Horsthemke B,Saitoh S,Niikawa N,Ledbetter SA,Greenberg F,Chinault AC,Ledbetter DH.Molecular dissection of the Prader-Willi/Angelman syndrome region(15q11-13)by YAC cloning and FISH analysis.Hum Mol Genet,1992,1:417–425
    39 Wagstaff J,Knoll JH,Glatt KA,Shugart YY,Sommer A,Lalande M.Maternal but not paternal transmission of 15q11-13-linked nondeletion angelman syndrome leads to phenotypic expression.Nat Genet,1992,1:291–294
    40 Pembrey M,Fennell SJ,van den Berghe J,Fitchett M,Summers D,Butler L,Clarke C,Griffiths M,Thompson E,Super M.The association of Angelman’s syndrome with deletions within 15q11-13.J Med Genet,1989,26:73–77
    41 Smith JC,Webb T,Pembrey ME,Nichols M,Malcolm S.Maternal origin of deletion 15q11-13 in 25/25 cases of angelman syndrome.Hum Genet,1992,88:376–378
    42 Tamada K,Tomonaga S,Hatanaka F,Nakai N,Takao K,Miyakawa T,Nakatani J,Takumi T.Decreased exploratory activity in a mouse model of 15q duplication syndrome;implications for disturbance of serotonin signaling.PLo S One,2010,5:e15126
    43 Nakatani J,Tamada K,Hatanaka F,Ise S,Ohta H,Inoue K,Tomonaga S,Watanabe Y,Chung YJ,Banerjee R,Iwamoto K,Kato T,Okazawa M,Yamauchi K,Tanda K,Takao K,Miyakawa T,Bradley A,Takumi T.Abnormal behavior in a chromosomeengineered mouse model for human 15q11-13 duplication seen in autism.Cell,2009,137:1235–1246
    44 Bhakar AL,Dolen G,Bear MF.The pathophysiology of fragile X(and what it teaches us about synapses).Annu Rev Neurosci,2012,35 :417–443
    45 Hagerman RJ,Jackson AW 3rd,Levitas A,Rimland B,Braden M.An analysis of autism in fifty males with the fragile X syndrome.Am J Med Genet,1986,23:359–374
    46 Wang LW,Berry-Kravis E,Hagerman RJ.Fragile X:leading the way for targeted treatments in autism.Neurotherapeutics,2010,7:264 –274
    47 Fu YH,Kuhl DP,Pizzuti A,Pieretti M,Sutcliffe JS,Richards S,Verkerk AJ,Holden JJ,Fenwick RG Jr,Warren ST,Oostra BA,Nelson DL,Thomas Caskey C.Variation of the CGG repeat at the fragile X site results in genetic instability:resolution of the Sherman paradox.Cell,1991,67:1047–1058
    48 Pieretti M,Zhang FP,Fu YH,Warren ST,Oostra BA,Caskey CT,Nelson DL.Absence of expression of the FMR-1 gene in fragile X syndrome.Cell,1991,66:817–822
    49 Dolen G,Osterweil E,Rao BS,Smith GB,Auerbach BD,Chattarji S,Bear MF.Correction of fragile X syndrome in mice.Neuron,2007,56 :955–962
    50 Osterweil EK,Krueger DD,Reinhold K,Bear MF.Hypersensitivity to m Glu R5 and ERK1/2 leads to excessive protein synthesis in the hippocampus of a mouse model of fragile X syndrome.J Neurosci,2010,30:15616–15627
    51 Liu ZH,Huang T,Smith CB.Lithium reverses increased rates of cerebral protein synthesis in a mouse model of fragile X syndrome.Neurobiol Dis,2012,45:1145–1152
    52 Thomas AM,Bui N,Graham D,Perkins JR,Yuva-Paylor LA,Paylor R.Genetic reduction of group 1 metabotropic glutamate receptors alters select behaviors in a mouse model for fragile X syndrome.Behav Brain Res,2011,223:310–321
    53 Spencer CM,Alekseyenko O,Serysheva E,Yuva-Paylor LA,Paylor R.Altered anxiety-related and social behaviors in the FMR1knockout mouse model of fragile X syndrome.Genes Brain Behav,2005,4:420–430
    54 Spencer CM,Graham DF,Yuva-Paylor LA,Nelson DL,Paylor R.Social behavior in Fmr1 knockout mice carrying a human FMR1transgene.Behav Neurosci,2008,122:710–715
    55 Min WW,Yuskaitis CJ,Yan Q,Sikorski C,Chen S,Jope RS,Bauchwitz RP.Elevated glycogen synthase kinase-3 activity in Fragile X mice:key metabolic regulator with evidence for treatment potential.Neuropharmacology,2009,56:463–472
    56 Yan QJ,Rammal M,Tranfaglia M,Bauchwitz RP.Suppression of two major Fragile X Syndrome mouse model phenotypes by the m Glu R5 antagonist MPEP.Neuropharmacology,2005,49:1053–1066
    57 Pan L,Broadie KS.Drosophila fragile X mental retardation protein and metabotropic glutamate receptor A convergently regulate the synaptic ratio of ionotropic glutamate receptor subclasses.J Neurosci,2007,27:12378–12389
    58 Pan L,Woodruff E 3rd,Liang P,Broadie K.Mechanistic relationships between Drosophila Fragile X mental retardation protein and metabotropic glutamate receptor A signaling.Mol Cell Neurosci,2008,37:747–760
    59 Repicky S,Broadie K.Metabotropic glutamate receptor-mediated use-dependent down-regulation of synaptic excitability involves the Fragile X mental retardation protein.J Neurophysiol,2009,101:672 –687
    60 Gasparini F,Lingenhohl K,Stoehr N,Flor PJ,Heinrich M,Vranesic I,Biollaz M,Allgeier H,Heckendorn R,Urwyler S,Varney MA,Johnson EC,Hess SD,Rao SP,Sacaan AI,Santori EM,Veli?elebi G,Kuhn R.2-methyl-6-(phenylethynyl)-pyridine(MPEP),a potent,selective and systemically active m Glu5 receptor antagonist.Neuropharmacology,1999,38:1493–1503
    61 Chuang SC,Zhao W,Bauchwitz R,Yan Q,Bianchi R,Wong RK.Prolonged epileptiform discharges induced by altered group I metabotropic glutamate receptor-mediated synaptic responses in hippocampal slices of a fragile X mouse model.J Neurosci,2005,25:8048–8055
    62 de Vrij FM,Levenga J,van der Linde HC,Koekkoek SK,De Zeeuw CI,Nelson DL,Oostra BA,Willemsen R.Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice.Neurobiol Dis,2008,31:127–132
    63 Aschrafi A,Cunningham BA,Edelman GM,Vanderklish PW.The fragile X mental retardation protein and group I metabotropic glutamate receptors regulate levels of m RNA granules in brain.Proc Natl Acad Sci USA,2005,102:2180–2185
    64 Mc Bride SM,Choi CH,Wang Y,Liebelt D,Braunstein E,Ferreiro D,Sehgal A,Siwicki KK,Dockendorff TC,Nguyen HT,Mc Donald TV,Jongens TA.Pharmacological rescue of synaptic plasticity,courtship behavior,and mushroom body defects in a Drosophila model offragile X syndrome.Neuron,2005,45:753–764
    65 Bolduc FV,Bell K,Cox H,Broadie KS,Tully T.Excess protein synthesis in Drosophila fragile X mutants impairs long-term memory.Nat Neurosci,2008,11:1143–1145
    66 Chang S,Bray SM,Li Z,Zarnescu DC,He C,Jin P,Warren ST.Identification of small molecules rescuing fragile X syndrome phenotypes in Drosophila.Nat Chem Biol,2008,4:256–263
    67 Tucker B,Richards RI,Lardelli M.Contribution of m Glu R and Fmr1functional pathways to neurite morphogenesis,craniofacial development and fragile X syndrome.Hum Mol Genet,2006,15:3446–3458
    68 Krueger DD,Bear MF.Toward fulfilling the promise of molecular medicine in fragile X syndrome.Annu Rev Med,2011,62:411–429
    69 Jacquemont S,Berry-Kravis E,Hagerman R,von Raison F,Gasparini F,Apostol G,Ufer M,Des Portes V,Gomez-Mancilla B.The challenges of clinical trials in fragile X syndrome.Psychopharmacology(Berl),2014,231:1237–1250
    70 Pop AS,Gomez-Mancilla B,Neri G,Willemsen R,Gasparini F.Fragile X syndrome:a preclinical review on metabotropic glutamate receptor 5(m Glu R5)antagonists and drug development.Psychopharmacology Berl),2014,231:1217–1226
    71 Ghosh A,Michalon A,Lindemann L,Fontoura P,Santarelli L.Drug discovery for autism spectrum disorder:challenges and opportunities.Nat Rev Drug Discov,2013,12:777–790
    72 Sudhof TC.Neuroligins and neurexins link synaptic function to cognitive disease.Nature,2008,455:903–911
    73 Lise MF,El-Husseini A.The neuroligin and neurexin families:from structure to function at the synapse.Cell Mol Life Sci,2006,63:1833–1849
    74 Comoletti D,Flynn RE,Boucard AA,Demeler B,Schirf V,Shi J,Jennings LL,Newlin HR,Südhof TC,Taylor P.Gene selection,alternative splicing,and post-translational processing regulate neuroligin selectivity forb-neurexins.Biochemistry,2006,45:12816–12827
    75 Arac D,Boucard AA,Ozkan E,Strop P,Newell E,Südhof TC,Brunger AT.Structures of neuroligin-1 and the neuroligin-1/neurexin-1bcomplex reveal specific protein-protein and protein-Ca2+interactions.Neuron,2007,56:992–1003
    76 Boucard AA,Chubykin AA,Comoletti D,Taylor P,Südhof TC.A splice code for trans-synaptic cell adhesion mediated by binding of neuroligin 1 toa-andb-neurexins.Neuron,2005,48:229–236
    77 Chubykin AA,Atasoy D,Etherton MR,Brose N,Kavalali ET,Gibson JR,Südhof TC.Activity-dependent validation of excitatory versus inhibitory synapses by neuroligin-1 versus neuroligin-2.Neuron,2007,54:919–931
    78 Zhang C,Atasoy D,Arac D,Yang X,Fucillo MV,Robison AJ,Ko J,Brunger AT,Südhof TC.Neurexins physically and functionally interact with GABAA receptors.Neuron,2010,66:403–416
    79 Ko J,Soler-Llavina GJ,Fuccillo MV,Malenka RC,Südhof TC.Neuroligins/LRRTMs prevent activity-and Ca2+/calmodulindependent synapse elimination in cultured neurons.J Cell Biol,2011,194 :323–334
    80 Varoqueaux F,Aramuni G,Rawson RL,Mohrmann R,Missler M,Gottmann K,Zhang W,Südhof TC,Brose N.Neuroligins determine synapse maturation and function.Neuron,2006,51:741–754
    81 Zhang W,Rohlmann A,Sargsyan V,Aramuni G,Hammer RE,Südhof TC,Missler M.Extracellular domains of alpha-neurexins participate in regulating synaptic transmission by selectively affecting N-and P/Q-type Ca2+channels.J Neurosci,2005,25:4330–4342
    82 Missler M,Zhang W,Rohlmann A,Kattenstroth G,Hammer RE,Gottmann K,Südhof TC.a-neurexins couple Ca2+channels to synaptic vesicle exocytosis.Nature,2003,423:939–948
    83 Kattenstroth G,Tantalaki E,Sudhof TC,Gottmann K,Missler M.Postsynaptic N-methyl-D-aspartate receptor function requiresa-neurexins.Proc Natl Acad Sci USA,2004,101:2607–2612
    84 Yan J,Noltner K,Feng J,Li W,Schroer R,Skinner C,Zeng W,chwartz CE,Sommer SS.Neurexin 1astructural variants associated with autism.Neurosci Lett,2008,438:368–370
    85 Feng J,Schroer R,Yan J,Song W,Yang C,Bockholt A,Cook EH Jr,Skinner C,Schwartz CE,Sommer SS.High frequency of neurexin 1bsignal peptide structural variants in patients with autism.Neurosci Lett,2006,409:10–13
    86 Camacho-Garcia RJ,Hervas A,Toma C,Balma?a N,Cormand B,Martinez-Mir A,Scholl FG.Rare variants analysis of neurexin-1bin autism reveals a novel start codon mutation affecting protein levels at synapses.Psychiatr Genet,2013,23:262–266
    87 Bena F,Bruno DL,Eriksson M,van Ravenswaaij-Arts C,Stark Z,Dijkhuizen T,Gerkes E,Gimelli S,Ganesamoorthy D,Thuresson AC,Labalme A,Till M,Bilan F,Pasquier L,Kitzis A,Dubourgm C,Rossi M,Bottani A,Gagnebin M,Sanlaville D,Gilbert-Dussardier B,Guipponi M,van Haeringen A,Kriek M,Ruivenkamp C,Antonarakis SE,Anderlid BM,Slater HR,Schoumans J.Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature.Am J Med Genet B Neuropsychiatr Genet,2013,162B:388–403
    88 Schaaf CP,Boone PM,Sampath S,Williams C,Bader PI,Mueller JM,Shchelochkov OA,Brown CW,Crawford HP,Phalen JA,Tartaglia NR,Evans P,Campbell WM,Tsai AC,Parsley L,Grayson SW,Scheuerle A,Luzzi CD,Thomas SK,Eng PA,Kang SH,Patel A,Stankiewicz P,Cheung SW.Phenotypic spectrum and genotypephenotype correlations of NRXN1 exon deletions.Eur J Hum Genet,2012,20:1240–1247
    89 Liu Y,Hu Z,Xun G,Peng Y,Lu L,Xu X,Xiong Z,Xia L,Liu D,Li W,Zhao J,Xia K.Mutation analysis of the NRXN1 gene in a Chinese autism cohort.J Psychiatr Res,2012,46:630–634
    90 Zweier C,de Jong EK,Zweier M,Orrico A,Ousager LB,Collins AL,Bijlsma EK,Oortveld MA,Ekici AB,Reis A,Schenck A,Rauch A.CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in Drosophila.Am J Hum Genet,2009,85:655 –666
    91 Autism Genome Project Consortium,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,Mc Mahon WM,Minshew N,Munson J,Korvatska E,Rodier PM,Schellenberg GD,Smith M,Spence MA,Stodgell C,Tepper PG,Wijsman EM,Yu CE,RogéB,Mantoulan C,Wittemeyer K,Poustka A,Felder B,Klauck SM,Schuster C,Poustka F,B?lte S,Feineis-Matthews S,Herbrecht E,Schm?tzer 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,Hijmans C,Staal WG,Baird G,Bolton PF,Rutter ML,Weisblatt E,Green J,Aldred C,Wilkinson JA,Pickles A,Le Couteur A,Berney T,Mc Conachie H,Bailey AJ,Francis K,Honeyman G,Hutchinson A,Parr JR,Wallace S,Monaco AP,Barnby G,Kobayashi K,Lamb JA,Sousa I,Sykes N,Cook EH,Guter SJ,Leventhal BL,Salt J,Lord C,Corsello C,Hus V,Weeks DE,Volkmar F,Tauber M,Fombonne E,Shih A,Meyer KJ.Mapping autism risk loci using genetic linkage and chromosomal rearrangements.Nat Genet,2007,39:319–328
    92 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.Structural variation of chromosomes inautism spectrum disorder.Am J Hum Genet,2008,82:477–488
    93 Morrow EM,Yoo SY,Flavell SW,Kim TK,Lin Y,Hill RS,Mukaddes NM,Balkhy S,Gascon G,Hashmi A,Al-Saad S,Ware J,Joseph RM,Greenblatt R,Gleason D,Ertelt JA,Apse KA,Bodell A,Partlow JN,Barry B,Yao H,Markianos K,Ferland RJ,Greenberg ME,Walsh CA.Identifying autism loci and genes by tracing recent shared ancestry.Science,2008,321:218–223
    94 Camacho-Garcia RJ,Planelles MI,Margalef M,Pecero ML,Martínez-Leal R,Aguilera F,Vilella E,Martinez-Mir A,Scholl FG.Mutations affecting synaptic levels of neurexin-1bin autism and mental retardation.Neurobiol Dis,2012,47:135–143
    95 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,Barthélémy C,Moraine C,Briault S.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,2004,74:552–557
    96 Jamain S,Quach H,Betancur C,R?stam M,Colineaux C,Gillberg IC,Soderstrom H,Giros B,Leboyer M,Gillberg C,Bourgeron T;Paris Autism Research International Sibpair Study.Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism.Nat Genet,2003,34:27–29
    97 Zhang C,Milunsky JM,Newton S,Ko J,Zhao G,Maher TA,Tager-Flusberg H,Bolliger MF,Carter AS,Boucard AA,Powell CM,Südhof TC.A neuroligin-4 missense mutation associated with autism impairs neuroligin-4 folding and endoplasmic reticulum export.J Neurosci,2009,29:10843–10854
    98 Avdjieva-Tzavella DM,Todorov TP,Todorova AP,Kirov AV,Hadjidekova SP,Rukova BB,Litvinenko IO,Hristova-Naydenova DN,Tincheva RS,Toncheva DI.Analysis of the genes encoding neuroligins NLGN3 and NLGN4 in Bulgarian patients with autism.Genet Couns,2012,23:505–511
    99 Chih B,Afridi SK,Clark L,Scheiffele P.Disorder-associated mutations lead to functional inactivation of neuroligins.Hum Mol Genet,2004,13:1471–1477
    100 Yan J,Oliveira G,Coutinho A,Yang C,Feng J,Katz C,Sram J,Bockholt A,Jones IR,Craddock N,Cook EH Jr,Vicente A,Sommer SS.Analysis of the neuroligin 3 and 4 genes in autism and other neuropsychiatric patients.Mol Psychiatry,2005,10:329–332
    101 Yanagi K,Kaname T,Wakui K,Hashimoto O,Fukushima Y,Naritomi K.Identification of four novel synonymous substitutions in the X-linked genes neuroligin 3 and neuroligin 4X in Japanese patients with autistic spectrum disorder.Autism Res Treat,2012,2012:724072
    102 Millson A,Lagrave D,Willis MJ,Rowe LR,Lyon E,South ST.Chromosomal loss of 3q26.3-3q26.32,involving a partial neuroligin1 deletion,identified by genomic microarray in a child with microcephaly,seizure disorder,and severe intellectual disability.Am J Med Genet A,2012,158A:159–165
    103 Pampanos A,Volaki K,Kanavakis E,Papandreou O,Youroukos S,Thomaidis L,Karkelis S,Tzetis M,Kitsiou-Tzeli S.A substitution involving the NLGN4 gene associated with autistic behavior in the Greek population.Genet Test Mol Biomarkers,2009,13:611–615
    104 Daoud H,Bonnet-Brilhault F,Védrine S,Demattéi MV,Vourc’h P,Bayou N,Andres CR,Barthélémy C,Laumonnier F,Briault S.Autism and nonsyndromic mental retardation associated with a de novo mutation in the NLGN4X gene promoter causing an increased expression level.Biol Psychiatry,2009,66:906–910
    105 Yan J,Feng J,Schroer R,Li W,Skinner C,Schwartz CE,Cook EH Jr,Sommer SS.Analysis of the neuroligin 4Y gene in patients with autism.Psychiatr Genet,2008,18:204–207
    106 Lawson-Yuen A,Saldivar JS,Sommer S,Picker J.Familial deletion within NLGN4 associated with autism and tourette syndrome.Eur J Hum Genet,2008,16:614–618
    107 Macarov M,Zeigler M,Newman JP,Strich D,Sury V,Tennenbaum A,Meiner V.Deletions of VCX-A and NLGN4:a variable phenotype including normal intellect.J Intellect Disabil Res,2007,51:329–333
    108 Chocholska S,Rossier E,Barbi G,Kehrer-Sawatzki H.Molecular cytogenetic analysis of a familial interstitial deletion Xp22.2-22.3with a highly variable phenotype in female carriers.Am J Med Genet A,2006,140:604–610
    109 Roberts JL,Hovanes K,Dasouki M,Manzardo AM,Butler MG.Chromosomal microarray analysis of consecutive individuals with autism spectrum disorders or learning disability presenting for genetic ervices.Gene,2014,535:70–78
    110 Talebizadeh Z,Lam DY,Theodoro MF,Bittel DC,Lushington GH,Butler MG.Novel splice isoforms for NLGN3 and NLGN4 with possible implications in autism.J Med Genet,2006,43:e21
    111 Grayton HM,Missler M,Collier DA,Fernandes C.Altered social behaviours in neurexin 1aknockout mice resemble core symptoms in neurodevelopmental disorders.PLo S One,2013,8:e67114
    112 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.Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism.Proc Natl Acad Sci USA,2008,105:1710–1715
    113 Foldy C,Malenka RC,Sudhof TC.Autism-associated neuroligin-3mutations commonly disrupt tonic endocannabinoid signaling.Neuron,2013,78:498–509
    114 Tabuchi K,Blundell J,Etherton MR,Hammer RE,Liu X,Powell CM,Südhof TC.A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice.Science,2007,318 :71–76
    115 Naisbitt S,Kim E,Tu JC,Xiao B,Sala C,Valtschanoff J,Weinberg RJ,Worley PF,Sheng M.Shank,a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin.Neuron,1999,23:569–582
    116 Durand CM,Betancur C,Boeckers TM,Bockmann J,Chaste P,Fauchereau F,Nygren G,Rastam M,Gillberg IC,Anckars?ter H,Sponheim E,Goubran-Botros H,Delorme R,Chabane N,Mouren-Simeoni MC,de Mas P,Bieth E,RogéB,Héron D,Burglen L,Gillberg C,Leboyer M,Bourgeron T.Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders.Nat Genet,2007,39:25–27
    117 Moessner R,Marshall CR,Sutcliffe JS,Skaug J,Pinto D,Vincent J,Zwaigenbaum L,Fernandez B,Roberts W,Szatmari P,Scherer SW.Contribution of SHANK3 mutations to autism spectrum disorder.Am J Hum Genet,2007,81:1289–1297
    118 Gauthier J,Spiegelman D,Piton A,Lafrenière RG,Laurent S,St-Onge J,Lapointe L,Hamdan FF,Cossette P,Mottron L,Fombonne E,Joober R,Marineau C,Drapeau P,Rouleau GA.Novel de novo SHANK3 mutation in autistic patients.Am J Med Genet B Neuropsychiatr Genet,2009,150B:421–424
    119 Waga C,Okamoto N,Ondo Y,Fukumura-Kato R,Goto Y,Kohsaka S,Uchino S.Novel variants of the SHANK3 gene in Japanese autistic patients with severe delayed speech development.Psychiatr Genet,2011,21:208–211
    120 Guilmatre A,Huguet G,Delorme R,Bourgeron T.The emerging role of SHANK genes in neuropsychiatric disorders.Dev Neurobiol,2014,74 :113–122
    121 Uchino S,Waga C.SHANK3 as an autism spectrum disorder-associated gene.Brain Dev,2013,35:106–110
    122 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,B?lte 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,LotspeichL,Lund SC,Maestrini E,Mahoney W,Mantoulan C,Marshall CR,Mc Conachie H,Mc Dougle CJ,Mc Grath J,Mc Mahon 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,Piven J,Ponting CP,Posey DJ,Poustka A,Poustka F,Prasad A,Ragoussis J,Renshaw K,Rickaby J,Roberts W,Roeder K,Roge B,Rutter ML,Bierut LJ,Rice JP,Salt J,Sansom K,Sato D,Segurado R,Sequeira AF,Senman L,Shah N,Sheffield VC,Soorya L,Sousa I,Stein O,Sykes N,Stoppioni V,Strawbridge C,Tancredi R,Tansey K,Thiruvahindrapduram B,Thompson AP,Thomson S,Tryfon A,Tsiantis J,Van Engeland H,Vincent JB,Volkmar F,Wallace S,Wang K,Wang Z,Wassink TH,Webber C,Weksberg R,Wing K,Wittemeyer K,Wood S,Wu J,Yaspan BL,Zurawiecki D,Zwaigenbaum L,Buxbaum JD,Cantor RM,Cook EH,Coon H,Cuccaro ML,Devlin B,Ennis S,Gallagher L,Geschwind DH,Gill M,Haines JL,Hallmayer J,Miller J,Monaco AP,Nurnberger JI Jr,Paterson AD,Pericak-Vance MA,Schellenberg GD,Szatmari P,Vicente AM,Vieland VJ,Wijsman EM,Scherer SW,Sutcliffe JS,Betancur C.Functional impact of global rare copy number variation in autism spectrum disorders.Nature,2010,466:368–372
    123 Berkel S,Marshall CR,Weiss B,Howe J,Roeth R,Moog U,Endris V,Roberts W,Szatmari P,Pinto D,Bonin M,Riess A,Engels H,Sprengel R,Scherer SW,Rappold GA.Mutations in the SHANK2synaptic scaffolding gene in autism spectrum disorder and mental retardation.Nat Genet,2010,42:489–491
    124 Leblond CS,Heinrich J,Delorme R,Proepper C,Betancur C,Huguet G,Konyukh M,Chaste P,Ey E,Rastam M,Anckars?ter H,Nygren G,Gillberg IC,Melke J,Toro R,Regnault B,Fauchereau F,Mercati O,Lemière N,Skuse D,Poot M,Holt R,Monaco AP,J?rvel?I,Kantoj?rvi K,Vanhala R,Curran S,Collier DA,Bolton P,Chiocchetti A,Klauck SM,Poustka F,Freitag CM,Waltes R,Kopp M,Duketis E,Bacchelli E,Minopoli F,Ruta L,Battaglia A,Mazzone L,Maestrini E,Sequeira AF,Oliveira B,Vicente A,Oliveira G,Pinto D,Scherer SW,Zelenika D,Delepine M,Lathrop M,Bonneau D,Guinchat V,Devillard F,Assouline B,Mouren MC,Leboyer M,Gillberg C,Boeckers TM,Bourgeron T.Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders.PLo S Genet,2012,8:e1002521
    125 Sato D,Lionel AC,Leblond CS,Prasad A,Pinto D,Walker S,O’Connor I,Russell C,Drmic IE,Hamdan FF,Michaud JL,Endris V,Roeth R,Delorme R,Huguet G,Leboyer M,Rastam M,Gillberg C,Lathrop M,Stavropoulos DJ,Anagnostou E,Weksberg R,Fombonne E,Zwaigenbaum L,Fernandez BA,Roberts W,Rappold GA,Marshall CR,Bourgeron T,Szatmari P,Scherer SW.SHANK1deletions in males with autism spectrum disorder.Am J Hum Genet,2012,90:879–887
    126 Peca J,Feliciano C,Ting JT,Wang W,Wells MF,Venkatraman TN,Lascola CD,Fu Z,Feng G.Shank3 mutant mice display autistic-like behaviours and striatal dysfunction.Nature,2011,472:437–442
    127 Yang M,Bozdagi O,Scattoni ML,W?hr M,Roullet FI,Katz AM,Abrams DN,Kalikhman D,Simon H,Woldeyohannes L,Zhang JY,Harris MJ,Saxena R,Silverman JL,Buxbaum JD,Crawley JN.Reduced excitatory neurotransmission and mild autism-relevant phenotypes in adolescent Shank3 null mutant mice.J Neurosci,2012,32 :6525–6541
    128 Neul JL,Kaufmann WE,Glaze DG,Christodoulou J,Clarke AJ,Bahi-Buisson N,Leonard H,Bailey ME,Schanen NC,Zappella M,Renieri A,Huppke P,Percy AK;Rett Search Consortium.Rett syndrome:revised diagnostic criteria and nomenclature.Ann Neurol,2010,68:944–950
    129 Amir RE,Van den Veyver IB,Wan M,Tran CQ,Francke U,Zoghbi HY.Rett syndrome is caused by mutations in X-linked MECP2,encoding methyl-Cp G-binding protein 2.Nat Genet,1999,23:185 –188
    130 Nagarajan RP,Hogart AR,Gwye Y,Martin MR,La Salle JM.Reduced Me CP2 expression is frequent in autism frontal cortex and correlates with aberrant MECP2 promoter methylation.Epigenetics,2006,1:e1–e11
    131 Percy AK.Rett syndrome:exploring the autism link.Arch Neurol,2011,68:985–989
    132 Castro J,Mellios N,Sur M.Mechanisms and therapeutic challenges in autism spectrum disorders:insights from rett syndrome.Curr Opin Neurol,2013,26:154–159
    133 Van Esch H,Bauters M,Ignatius J,Jansen M,Raynaud M,Hollanders K,Lugtenberg D,Bienvenu T,Jensen LR,Gecz J,Moraine C,Marynen P,Fryns JP,Froyen G.Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males.Am J Hum Genet,2005,77 :442–453
    134 Meins M,Lehmann J,Gerresheim F,Herchenbach J,Hagedorn M,Hameister K,Epplen JT.Submicroscopic duplication in Xq28 causes increased expression of the MECP2 gene in a boy with severe mental retardation and features of Rett syndrome.J Med Genet,2005,42:e12
    135 del Gaudio D,Fang P,Scaglia F,Ward PA,Craigen WJ,Glaze DG,Neul JL,Patel A,Lee JA,Irons M,Berry SA,Pursley AA,Grebe TA,Freedenberg D,Martin RA,Hsich GE,Khera JR,Friedman NR,Zoghbi HY,Eng CM,Lupski JR,Beaudet AL,Cheung SW,Roa BB.Increased MECP2 gene copy number as the result of genomic duplication in neurodevelopmentally delayed males.Genet Med,2006,8:784–792
    136 Carney RM,Wolpert CM,Ravan SA,Shahbazian M,Ashley-Koch A,Cuccaro ML,Vance JM,Pericak-Vance MA.Identification of Me CP2 mutations in a series of females with autistic disorder.Pediatr Neurol,2003,28:205–211
    137 Beyer KS,Blasi F,Bacchelli E,Klauck SM,Maestrini E,Poustka A;International Molecular Genetic Study of Autism Consortium(IMGSAC).Mutation analysis of the coding sequence of the MECP2gene in infantile autism.Hum Genet,2002,111:305–309
    138 Lam CW,Yeung WL,Ko CH,Poon PM,Tong SF,Chan KY,Lo IF,Chan LY,Hui J,Wong V,Pang CP,Lo YM,Fok TF.Spectrum of mutations in the MECP2 gene in patients with infantile autism and Rett syndrome.J Med Genet,2000,37:E41
    139 Chapleau CA,Calfa GD,Lane MC,Albertson AJ,Larimore JL,Kudo S,Armstrong DL,Percy AK,Pozzo-Miller L.Dendritic spine pathologies in hippocampal pyramidal neurons from Rett syndrome brain and after expression of Rett-associated MECP2 mutations.Neurobiol Dis,2009,35:219–233
    140 Chapleau CA,Boggio EM,Calfa G,Percy AK,Giustetto M,Pozzo-Miller L.Hippocampal CA1 pyramidal neurons of Mecp2mutant mice show a dendritic spine phenotype only in the presymptomatic stage.Neural Plast,2012,2012:976164
    141 Smrt RD,Eaves-Egenes J,Barkho BZ,Santistevan NJ,Zhao C,Aimone JB,Gage FH,Zhao X.Mecp2 deficiency leads to delayed maturation and altered gene expression in hippocampal neurons.Neurobiol Dis,2007,27:77–89
    142 Belichenko PV,Wright EE,Belichenko NP,Masliah E,Li HH,Mobley WC,Francke U.Widespread changes in dendritic and axonal morphology in Mecp2-mutant mouse models of Rett syndrome:evidence for disruption of neuronal networks.J Comp Neurol,2009,514 :240–258
    143 Nan X,Ng HH,Johnson CA,Laherty CD,Turner BM,Eisenman RN,Bird A.Transcriptional repression by the methyl-Cp G-binding protein Me CP2 involves a histone deacetylase complex.Nature,1998,393 :386–389
    144 Jones PL,Veenstra GJ,Wade PA,Vermaak D,Kass SU,Landsberger N,Strouboulis J,Wolffe AP.Methylated DNA and Me CP2 recruit histone deacetylase to repress transcription.Nat Genet,1998,19:187–191
    145 Chahrour M,Jung SY,Shaw C,Zhou X,Wong ST,Qin J,Zoghbi HY.Me CP2,a key contributor to neurological disease,activates and represses transcription.Science,2008,320:1224–1229
    146 Tao J,Hu K,Chang Q,Wu H,Sherman NE,Martinowich K,Klose RJ,Schanen C,Jaenisch R,Wang W,Sun YE.Phosphorylation of Me CP2 at Serine 80 regulates its chromatin association and neurological function.Proc Natl Acad Sci USA,2009,106:4882–4887
    147 Chao HT,Zoghbi HY.The yin and yang of Me CP2 phosphorylation.Proc Natl Acad Sci USA,2009,106:4577–4578
    148 Moretti P,Bouwknecht JA,Teague R,Paylor R,Zoghbi HY.Abnormalities of social interactions and home-cage behavior in a mouse model of Rett syndrome.Hum Mol Genet,2005,14:205–220
    149 Fyffe SL,Neul JL,Samaco RC,Chao HT,Ben-Shachar S,Moretti P,Mc Gill BE,Goulding EH,Sullivan E,Tecott LH,Zoghbi HY.Deletion of Me CP2 in Sim1-expressing neurons reveals a critical role for Me CP2 in feeding behavior,aggression,and the response to stress.Neuron,2008,59:947–958
    150 Liao W,Gandal MJ,Ehrlichman RS,Siegel SJ,Carlson GC.Me CP2+/-mouse model of RTT reproduces auditory phenotypes associated with Rett syndrome and replicate select EEG endophenotypes of autism spectrum disorder.Neurobiol Dis,2012,46 :88–92
    151 Lonetti G,Angelucci A,Morando L,Boggio EM,Giustetto M,Pizzorusso T.Early environmental enrichment moderates the behavioral and synaptic phenotype of Me CP2 null mice.Biol Psychiatry,2010,67:657–665
    152 Nag N,Moriuchi JM,Peitzman CG,Ward BC,Kolodny NH,Berger-Sweeney JE.Environmental enrichment alters locomotor behaviour and ventricular volume in Mecp21lox mice.Behav Brain Res,2009,196:44–48
    153 Kondo M,Gray LJ,Pelka GJ,Christodoulou J,Tam PP,Hannan AJ.Environmental enrichment ameliorates a motor coordination deficit in a mouse model of Rett syndrome—Mecp2 gene dosage effects and BDNF expression.Eur J Neurosci,2008,27:3342–3350
    154 Buxbaum JD,Silverman JM,Smith CJ,Greenberg DA,Kilifarski M,Reichert J,Cook EH Jr,Fang Y,Song CY,Vitale R.Association between a GABRB3 polymorphism and autism.Mol Psychiatry,2002,7 :311–316
    155 Kim SA,Kim JH,Park M,Cho IH,Yoo HJ.Association of GABRB3polymorphisms with autism spectrum disorders in Korean trios.Neuropsychobiology,2006,54:160–165
    156 Menold MM,Shao Y,Wolpert CM,Donnelly SL,Raiford KL,Martin ER,Ravan SA,Abramson RK,Wright HH,Delong GR,Cuccaro ML,Pericak-Vance MA,Gilbert JR.Association analysis of chromosome 15 GABAA receptor subunit genes in autistic disorder.J Neurogenet,2001,15:245–259
    157 Solis-Anez E,Delgado-Luengo W,Borjas-Fuentes L,Zabala W,Arráiz N,Pineda L,Portillo MG,González-Ferrer S,Chacín JA,Pe?a J,Montiel C,Morales A,Rojas de Atencio A,Ca?izales J,González R,Miranda LE,Abreu N,Delgado J.Molecular analysis of the GABRB3 gene in autistic patients:an exploratory study.Invest Clin,2007,48:225–242
    158 Yoo HK,Chung S,Hong JP,Kim BN,Cho SC.Microsatellite marker in gamma-aminobutyric acid-a receptor beta 3 subunit gene and autism spectrum disorders in Korean trios.Yonsei Med J,2009,50:304 –306
    159 Delahanty RJ,Kang JQ,Brune CW,Kistner EO,Courchesne E,Cox NJ,Cook EH Jr,Macdonald RL,Sutcliffe JS.Maternal transmission of a rare GABRB3 signal peptide variant is associated with autism.Mol Psychiatry,2011,16:86–96
    160 Hogart A,Nagarajan RP,Patzel KA,Yasui DH,Lasalle JM.15 q11-13 GABAA receptor genes are normally biallelically expressed in brain yet are subject to epigenetic dysregulation in autismspectrum disorders.Hum Mol Genet,2007,16:691–703
    161 Homanics GE,De Lorey TM,Firestone LL,Quinlan JJ,Handforth A,Harrison NL,Krasowski MD,Rick CE,Korpi ER,M?kel?R,Brilliant MH,Hagiwara N,Ferguson C,Snyder K,Olsen RW.Mice devoid ofg-aminobutyrate type A receptorb3 subunit have epilepsy,cleft palate,and hypersensitive behavior.Proc Natl Acad Sci USA,1997,94:4143–4148
    162 De Lorey TM,Handforth A,Anagnostaras SG,Homanics GE,Minassian BA,Asatourian A,Fanselow MS,Delgado-Escueta A,Ellison GD,Olsen RW.Mice lacking theb3 subunit of the GABAA receptor have the epilepsy phenotype and many of the behavioral characteristics of Angelman syndrome.J Neurosci,1998,18:8505–8514
    163 De Lorey TM,Sahbaie P,Hashemi E,Homanics GE,Clark JD.Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors,deficits in non-selective attention and hypoplasia of cerebellar vermal lobules:a potential model of autism spectrum disorder.Behav Brain Res,2008,187:207–220
    164 Ferguson C,Hardy SL,Werner DF,Hileman SM,Delorey TM,Homanics GE.New insight into the role of theb3 subunit of the GABAA-R in development,behavior,body weight regulation,and anesthesia revealed by conditional gene knockout.BMC Neurosci,2007,8:85
    165 Collins AL,Ma D,Whitehead PL,Martin ER,Wright HH,Abramson RK,Hussman JP,Haines JL,Cuccaro ML,Gilbert JR,Pericak-Vance MA.Investigation of autism and GABA receptor subunit genes in multiple ethnic groups.Neurogenetics,2006,7:167–174
    166 Ma DQ,Whitehead PL,Menold MM,Martin ER,Ashley-Koch AE,Mei H,Ritchie MD,Delong GR,Abramson RK,Wright HH,Cuccaro ML,Hussman JP,Gilbert JR,Pericak-Vance MA.Identification of significant association and gene-gene interaction of GABA receptor subunit genes in autism.Am J Hum Genet,2005,77:377 –388
    167 Dhossche D,Applegate H,Abraham A,Maertens P,Bland L,Bencsath A,Martinez J.Elevated plasma gamma-aminobutyric acid(GABA)levels in autistic youngsters:stimulus for a GABA hypothesis of autism.Med Sci Monit,2002,8:PR1–PR6
    168 Rolf LH,Haarmann FY,Grotemeyer KH,Kehrer H.Serotonin and amino acid content in platelets of autistic children.Acta Psychiatr Scand,1993,87:312–316
    169 Blatt GJ,Fitzgerald CM,Guptill JT,Booker AB,Kemper TL,Bauman ML.Density and distribution of hippocampal neurotransmitter receptors in autism:an autoradiographic study.J Autism Dev Disord,2001,31:537–543
    170 Fatemi SH,Reutiman TJ,Folsom TD,Rooney RJ,Patel DH,Thuras PD.m RNA and protein levels for GABAAa4,a5,b1 and GABAB R1 receptors are altered in brains from subjects with autism.J Autism Dev Disord,2010,40:743–750
    171 Fatemi SH,Reutiman TJ,Folsom TD,Thuras PD.GABAA receptor downregulation in brains of subjects with autism.J Autism Dev Disord,2009,39:223–230
    172 Oblak AL,Gibbs TT,Blatt GJ.Reduced GABAA receptors and benzodiazepine binding sites in the posterior cingulate cortex and fusiform gyrus in autism.Brain Res,2011,1380:218–228
    173 Oblak A,Gibbs TT,Blatt GJ.Decreased GABAA receptors and benzodiazepine binding sites in the anterior cingulate cortex in autism.Autism Res,2009,2:205–219
    174 Ozonoff S,Iosif AM,Baguio F,Cook IC,Hill MM,Hutman T,Rogers SJ,Rozga A,Sangha S,Sigman M,Steinfeld MB,Young GS.A prospective study of the emergence of early behavioral signs of autism.J Am Acad Child Adolesc Psychiatry,2010,49:256–266.e1–e2
    175 Volkmar FR.Childhood disintegrative disorder:issues for DSM-IV.J Autism Dev Disord,1992,22:625–642
    176 Kern JK,Geier DA,Sykes LK,Geier MR.Evidence of neurodegeneration in autism spectrum disorder.Transl Neurodegener,2013,2:17
    177 Courchesne E,Pierce K,Schumann CM,Redcay E,Buckwalter JA,Kennedy DP,Morgan J.Mapping early brain development in autism.Neuron,2007,56:399–413
    178 Bailey A,Luthert P,Dean A,Harding B,Janota I,Montgomery M,Rutter M,Lantos P.A clinicopathological study of autism.Brain,1998,121:889–905
    179 Vargas DL,Nascimbene C,Krishnan C,Zimmerman AW,Pardo CA.Neuroglial activation and neuroinflammation in the brain of patients with autism.Ann Neurol,2005,57:67–81
    180 Whitney ER,Kemper TL,Bauman ML,Rosene DL,Blatt GJ.Cerebellar Purkinje cells are reduced in a subpopulation of autistic brains:a stereological experiment using calbindin-D28K.Cerebellum,2008,7:406–416
    181 Andersen JK.Oxidative stress in neurodegeneration:cause or consequence?Nat Med,2004,10 Suppl:S18–S25
    182 Sajdel-Sulkowska EM,Xu M,Koibuchi N.Increase in cerebellar neurotrophin-3 and oxidative stress markers in autism.Cerebellum,2009,8:366–372
    183 Sajdel-Sulkowska EM,Xu M,Mc Ginnis W,Koibuchi N.Brain region-specific changes in oxidative stress and neurotrophin levels in autism spectrum disorders(ASD).Cerebellum,2011,10:43–48
    184 Chauhan A,Gu F,Essa MM,Wegiel J,Kaur K,Brown WT,Chauhan V.Brain region-specific deficit in mitochondrial electron transport chain complexes in children with autism.J Neurochem,2011,117:209 –220
    185 Frustaci A,Neri M,Cesario A,Adams JB,Domenici E,Dalla Bernardina B,Bonassi S.Oxidative stress-related biomarkers in autism:systematic review and meta-analyses.Free Radic Biol Med,2012,52:2128–2141
    186 Liu X,Solehdin F,Cohen IL,Gonzalez MG,Jenkins EC,Lewis ME,Holden JJ.Population-and family-based studies associate the MTHFR gene with idiopathic autism in simplex families.J Autism Dev Disord,2011,41:938–944
    187 Pasca SP,Dronca E,Kaucsar T,Craciun EC,Endreffy E,Ferencz BK,Iftene F,Benga I,Cornean R,Banerjee R,Dronca M.One carbon metabolism disturbances and the C677T MTHFR gene polymorphism in children with autism spectrum disorders.J Cell Mol Med,2009,13:4229–4238
    188 James SJ,Melnyk S,Jernigan S,Cleves MA,Halsted CH,Wong DH,Cutler P,Bock K,Boris M,Bradstreet JJ,Baker SM,Gaylor DW.Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism.Am J Med Genet B Neuropsychiatr Genet,2006,141B:947–956
    189 Mohammad NS,Jain JM,Chintakindi KP,Singh RP,Naik U,Akella RR.Aberrations in folate metabolic pathway and altered susceptibility to autism.Psychiatr Genet,2009,19:171–176
    190 Buyske S,Williams TA,Mars AE,Stenroos ES,Ming SX,Wang R,Sreenath M,Factura MF,Reddy C,Lambert GH,Johnson WG.Analysis of case-parent trios at a locus with a deletion allele:association of GSTM1 with autism.BMC Genet,2006,7:8
    191 Leoni V.The effect of apolipoprotein E(Apo E)genotype on biomarkers of amyloidogenesis,tau pathology and neurodegeneration in Alzheimer’s disease.Clin Chem Lab Med,2011,49:375–383
    192 Obulesu M,Somashekhar R,Venu R.Genetics of Alzheimer’s disease:an insight into presenilins and apolipoprotein E instigated neurodegeneration.Int J Neurosci,2011,121:229–236
    193 Liu CC,Kanekiyo T,Xu H,Bu G.Apolipoprotein E and Alzheimer disease:risk,mechanisms and therapy.Nat Rev Neurol,2013,9:106 –118
    194 Corder EH,Lannfelt L,Bogdanovic N,Fratiglioni L,Mori H.The role of APOE polymorphisms in late-onset dementias.Cell Mol Life Sci,1998,54:928–934
    195 Giunco CT,de Oliveira AB,Carvalho-Salles AB,Souza DS,Silva AE,da Rocha SS,Fett-Conte AC.Association between APOE polymorphisms and predisposition for autism.Psychiatr Genet,2009,19:338
    196 Persico AM,D’Agruma L,Zelante L,Militerni R,Bravaccio C,Schneider C,Melmed R,Trillo S,Montecchi F,Elia M,Palermo M,Rabinowitz D,Pascucci T,Puglisi-Allegra S,Reichelt KL,Muscarella L,Guarnieri V,Melgari JM,Conciatori M,Keller F.Enhanced APOE2 transmission rates in families with autistic probands.Psychiatr Genet,2004,14:73–82
    197 Bothwell M,Giniger E.Alzheimer’s disease:neurodevelopment converges with neurodegeneration.Cell,2000,102:271–273
    198 Knuesel I.Reelin-mediated signaling in neuropsychiatric and neurodegenerative diseases.Prog Neurobiol,2010,91:257–274
    199 Fatemi SH.Reelin glycoprotein:structure,biology and roles in health and disease.Mol Psychiatry,2005,10:251–257
    200 Kelemenova S,Schmidtova E,Ficek A,Celec P,Kubranska A,Ostatnikova D.Polymorphisms of candidate genes in Slovak autistic patients.Psychiatr Genet,2010,20:137–139
    201 Persico AM,D’Agruma L,Maiorano N,Totaro A,Militerni R,Bravaccio C,Wassink TH,Schneider C,Melmed R,Trillo S,Montecchi F,Palermo M,Pascucci T,Puglisi-Allegra S,Reichelt KL,Conciatori M,Marino R,Quattrocchi CC,Baldi A,Zelante L,Gasparini P,Keller F;Collaborative Linkage Study of Autism.Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder.Mol Psychiatry,2001,6:150–159
    202 Ashley-Koch A,Wolpert CM,Menold MM,Zaeem L,Basu S,Donnelly SL,Ravan SA,Powell CM,Qumsiyeh MB,Aylsworth AS,Vance JM,Gilbert JR,Wright HH,Abramson RK,De Long GR,Cuccaro ML,Pericak-Vance MA.Genetic studies of autistic disorder and chromosome 7.Genomics,1999,61:227–236
    203 International Molecular Genetic Study Of Autism Consortium.A full genome screen for autism with evidence for linkage to a region on chromosome 7q.Hum Mol Genet,1998,7:571–578
    204 Del Rio JA,Heimrich B,Borrell V,F?rster E,Drakew A,Alcántara S,Nakajima K,Miyata T,Ogawa M,Mikoshiba K,Derer P,Frotscher M,Soriano E.A role for Cajal-Retzius cells and reelin in the development of hippocampal connections.Nature,1997,385:70 –74
    205 Goffinet AM.Events governing organization of postmigratory neurons:studies on brain development in normal and reeler mice.Brain Res,1984,319:261–296
    206 Walsh DM,Minogue AM,Sala Frigerio C,Fadeeva JV,Wasco W,Selkoe DJ.The APP family of proteins:similarities and differences.Biochem Soc Trans,2007,35:416–420
    207 Zhang YW,Thompson R,Zhang H,Xu H.APP processing in Alzheimer’s disease.Mol Brain,2011,4:3
    208 Rohan de Silva HA,Jen A,Wickenden C,Jen LS,Wilkinson SL,Patel AJ.Cell-specific expression of beta-amyloid precursor protein isoform m RNAs and proteins in neurons and astrocytes.Brain Res Mol Brain Res,1997,47:147–156
    209 Zheng H,Koo EH.The amyloid precursor protein:beyond amyloid.Mol Neurodegener,2006,1:5
    210 Selkoe DJ.Biochemistry and molecular biology of amyloidb-protein and the mechanism of Alzheimer’s disease.Handb Clin Neurol,2008,89 :245–260
    211 Kamenetz F,Tomita T,Hsieh H,Seabrook G,Borchelt D,Iwatsubo T,Sisodia S,Malinow R.APP processing and synaptic function.Neuron,2003,37:925–937
    212 Frackowiak J,Mazur-Kolecka B,Schanen NC,Brown WT,Wegiel J.The link between intraneuronal N-truncated amyloid-bpeptide and oxidatively modified lipids in idiopathic autism and dup(15q11.2-q13)/autism.Acta Neuropathol Commun,2013,1:61
    213 Wegiel J,Frackowiak J,Mazur-Kolecka B,Schanen NC,Cook EH Jr,Sigman M,Brown WT,Kuchna I,Wegiel J,Nowicki K,Imaki H,Ma SY,Chauhan A,Chauhan V,Miller DL,Mehta PD,Flory M,Cohen IL,London E,Reisberg B,de Leon MJ,Wisniewski T.Abnormal intracellular accumulation and extracellular Abdeposition in idiopathic and Dup15q11.2-q13 autism spectrum disorders.PLo S One,2012,7:e35414
    214 Sokol DK,Chen D,Farlow MR,Dunn DW,Maloney B,Zimmer JA,Lahiri DK.High levels of Alzheimer beta-amyloid precursor protein(APP)in children with severely autistic behavior and aggression.J Child Neurol,2006,21:444–449
    215 Devlin B,Scherer SW.Genetic architecture in autism spectrum disorder.Curr Opin Genet Dev,2012,22:229–237
    216 Jamain S,Betancur C,Giros B,Leboyer M,Bourgeron T.Genetics of autism:from genome scans to candidate genes.Med Sci(Paris),2003,19 :1081–1090
    217 Klei L,Sanders SJ,Murtha MT,Hus V,Lowe JK,Willsey AJ,Moreno-De-Luca D,Yu TW,Fombonne E,Geschwind D,Grice DE,Ledbetter DH,Lord C,Mane SM,Martin CL,Martin DM,Morrow EM,Walsh CA,Melhem NM,Chaste P,Sutcliffe JS,State MW,Cook EH Jr,Roeder K,Devlin B.Common genetic variants,acting additively,are a major source of risk for autism.Mol Autism,2012,3:9
    218 Willsey AJ,Sanders SJ,Li M,Dong S,Tebbenkamp AT,Muhle RA,Reilly SK,Lin L,Fertuzinhos S,Miller JA,Murtha MT,Bichsel C,Niu W,Cotney J,Ercan-Sencicek AG,Gockley J,Gupta AR,Han W,He X,Hoffman EJ,Klei L,Lei J,Liu W,Liu L,Lu C,Xu X,Zhu Y,Mane SM,Lein ES,Wei L,Noonan JP,Roeder K,Devlin B,Sestan N,State MW.Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism.Cell,2013,155 :997–1007
    219 Parikshak NN,Luo R,Zhang A,Won H,Lowe JK,Chandran V,Horvath S,Geschwind DH.Integrative functional genomic analyses implicate specific molecular pathways and circuits in autism.Cell,2013,155:1008–1021

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700