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Autism spectrum disorders: autistic phenotypes and complicated mechanisms

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Abstract

Background

Autism spectrum disorder (ASD), a pervasive developmental neurological disorder, is characterized by impairments in social interaction and communication, and stereotyped, repetitive patterns of interests or behaviors. The mechanism of ASDs is complex, and genetic components and epigenetic modifications play important roles. In this review, we summarized the recent progresses of ASDs focusing on the genetic and epigenetic mechanisms. We also briefly discussed current animal models of ASD and the application of high-throughput sequencing technologies in studying ASD.

Data sources

Original research articles and literature reviews published in PubMed-indexed journals.

Results

Individuals with ASDs exhibit a set of phenotypes including neurological alteration. Genetic components including gene mutation, copy-number variations, and epigenetic modifications play important and diverse roles in ASDs. The establishment of animal models and development of new-generation sequencing technologies have contributed to reveal the complicated mechanisms underlying autistic phenotypes.

Conclusions

Dramatic progress has been made for understanding the roles of genetic and epigenetic components in ASD. Future basic and translational studies should be carried out towards those candidate therapeutic targets.

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References

  1. Kanner L. Autistic disturbances of affective contact. Acta Paedopsychiatr. 1968;35:100–36.

    PubMed  CAS  Google Scholar 

  2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Washington: American Psychiatric Publishing, Inc.; 2013.

    Book  Google Scholar 

  3. Lai MC, Lombardo MV, Baron-Cohen S. Autism. Lancet (London, England). 2014;383:896–910.

    Article  Google Scholar 

  4. Christensen DL, Baio J, Van Naarden Braun K, Bilder D, Charles J, Constantino JN, et al. Prevalence and characteristics of autism spectrum disorder among children aged 8 years—autism and developmental disabilities monitoring network, 11 sites, United States, 2012. Morb Mortal Wkly Rep Surveill Summ (Washington, DC: 2002). 2016;65:1–23.

    Google Scholar 

  5. Boomsma D, Busjahn A, Peltonen L. Classical twin studies and beyond. Nat Rev Genet. 2002;3:872–82.

    Article  PubMed  CAS  Google Scholar 

  6. Sandin S, Reichenberg A. Recurrence rates in autism spectrum disorders—reply. JAMA. 2014;312:1155.

    Article  PubMed  Google Scholar 

  7. Yuen RK, Thiruvahindrapuram B, Merico D, Walker S, Tammimies K, Hoang N, et al. Whole-genome sequencing of quartet families with autism spectrum disorder. Nat Med. 2015;21:185–91.

    Article  PubMed  CAS  Google Scholar 

  8. Kitzbichler MG, Khan S, Ganesan S, Vangel MG, Herbert MR, Hamalainen MS, et al. Altered development and multifaceted band-specific abnormalities of resting state networks in autism. Biol Psychiatry. 2015;77:794–804.

    Article  PubMed  Google Scholar 

  9. Hazlett HC, Gu H, Munsell BC, Kim SH, Styner M, Wolff JJ, et al. Early brain development in infants at high risk for autism spectrum disorder. Nature. 2017;542:348–51.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Chen JA, Penagarikano O, Belgard TG, Swarup V, Geschwind DH. The emerging picture of autism spectrum disorder: genetics and pathology. Annu Rev Pathol. 2015;10:111–44.

    Article  PubMed  CAS  Google Scholar 

  11. Casanova MF. Neuropathological and genetic findings in autism: the significance of a putative minicolumnopathy. Neurosci. 2006;12:435–41.

    Google Scholar 

  12. Courchesne E, Mouton PR, Calhoun ME, Semendeferi K, Ahrens-Barbeau C, Hallet MJ, et al. Neuron number and size in prefrontal cortex of children with autism. JAMA. 2011;306:2001–10.

    Article  PubMed  CAS  Google Scholar 

  13. Hutsler JJ, Zhang H. Increased dendritic spine densities on cortical projection neurons in autism spectrum disorders. Brain Res. 2010;1309:83–94.

    Article  PubMed  CAS  Google Scholar 

  14. Azmitia EC, Singh JS, Whitaker-Azmitia PM. Increased serotonin axons (immunoreactive to 5-HT transporter) in postmortem brains from young autism donors. Neuropharmacology. 2011;60:1347–54.

    Article  PubMed  CAS  Google Scholar 

  15. Varghese M, Keshav N, Jacot-Descombes S, Warda T, Wicinski B, Dickstein DL, et al. Autism spectrum disorder: neuropathology and animal models. Acta Neuropathol. 2017;134:537–66.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Jacot-Descombes S, Uppal N, Wicinski B, Santos M, Schmeidler J, Giannakopoulos P, et al. Decreased pyramidal neuron size in Brodmann areas 44 and 45 in patients with autism. Acta Neuropathol. 2012;124:67–79.

    Article  PubMed  CAS  Google Scholar 

  17. Pierce K, Haist F, Sedaghat F, Courchesne E. The brain response to personally familiar faces in autism: findings of fusiform activity and beyond. Brain. 2004;127:2703–16.

    Article  PubMed  Google Scholar 

  18. Kim HJ, Cho MH, Shim WH, Kim JK, Jeon EY, Kim DH, et al. Deficient autophagy in microglia impairs synaptic pruning and causes social behavioral defects. Mol Psychiatry. 2016;22:1576.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Wang Z, Hong Y, Zou L, Zhong R, Zhu B, Shen N, et al. Reelin gene variants and risk of autism spectrum disorders: an integrated meta-analysis. Am J Med Genet Part B Neuropsychiatr Genet. 2014;165:192–200.

    Article  CAS  Google Scholar 

  20. Monteiro P, Feng G. SHANK proteins: roles at the synapse and in autism spectrum disorder. Nat Rev Neurosci. 2017;18:147–57.

    Article  PubMed  CAS  Google Scholar 

  21. Leblond CS, Nava C, Polge A, Gauthier J, Huguet G, Lumbroso S, et al. Meta-analysis of SHANK mutations in autism spectrum disorders: a gradient of severity in cognitive impairments. PLoS Genet. 2014;10:e1004580.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Mei Y, Monteiro P, Zhou Y, Kim JA, Gao X, Fu Z, et al. Adult restoration of Shank3 expression rescues selective autistic-like phenotypes. Nature. 2016;530:481–4.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Zhou Y, Kaiser T, Monteiro P, Zhang X, Van der Goes MS, Wang D, et al. Mice with Shank3 mutations associated with ASD and Schizophrenia display both shared and distinct defects. Neuron. 2016;89:147–62.

    Article  PubMed  CAS  Google Scholar 

  24. Isshiki M, Tanaka S, Kuriu T, Tabuchi K, Takumi T, Okabe S. Enhanced synapse remodelling as a common phenotype in mouse models of autism. Nat Commun. 2014;5:4742.

    Article  PubMed  CAS  Google Scholar 

  25. Chanda S, Aoto J, Lee SJ, Wernig M, Sudhof TC. Pathogenic mechanism of an autism-associated neuroligin mutation involves altered AMPA-receptor trafficking. Mol Psychiatry. 2016;21:169–77.

    Article  PubMed  CAS  Google Scholar 

  26. Sudhof TC. Neuroligins and neurexins link synaptic function to cognitive disease. Nature. 2008;455:903–11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Grayton HM, Missler M, Collier DA, Fernandes C. Altered social behaviours in neurexin 1alpha knockout mice resemble core symptoms in neurodevelopmental disorders. PLoS One. 2013;8:e67114.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Dachtler J, Glasper J, Cohen RN, Ivorra JL, Swiffen DJ, Jackson AJ, et al. Deletion of alpha-neurexin II results in autism-related behaviors in mice. Transl Psychiatry. 2014;4:e484.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Chrobak AA, Soltys Z. Bergmann glia, long-term depression, and autism spectrum disorder. Mol Neurobiol. 2017;54:1156–66.

    Article  PubMed  CAS  Google Scholar 

  30. El-Ansary A, Al-Ayadhi L. GABAergic/glutamatergic imbalance relative to excessive neuroinflammation in autism spectrum disorders. J Neuroinflammation. 2014;11:189.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Russ SA, Larson K, Halfon N. A national profile of childhood epilepsy and seizure disorder. Pediatrics. 2012;129:256–64.

    Article  PubMed  Google Scholar 

  32. Reilly C, Atkinson P, Das KB, Chin RF, Aylett SE, Burch V, et al. Neurobehavioral comorbidities in children with active epilepsy: a population-based study. Pediatrics. 2014;133:e1586–93.

    Article  PubMed  Google Scholar 

  33. Amiet C, Gourfinkel-An I, Bouzamondo A, Tordjman S, Baulac M, Lechat P, et al. Epilepsy in autism is associated with intellectual disability and gender: evidence from a meta-analysis. Biol Psychiatry. 2008;64:577–82.

    Article  PubMed  Google Scholar 

  34. Lee BH, Smith T, Paciorkowski AR. Autism spectrum disorder and epilepsy: disorders with a shared biology. Epilepsy Behav. 2015;47:191–201.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Sanders SJ, He X, Willsey AJ, Ercan-Sencicek AG, Samocha KE, Cicek AE, et al. Insights into autism spectrum disorder genomic architecture and biology from 71 risk loci. Neuron. 2015;87:1215–33.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Belmonte MK, Bourgeron T. Fragile X syndrome and autism at the intersection of genetic and neural networks. Nat Neurosci. 2006;9:1221–5.

    Article  PubMed  CAS  Google Scholar 

  37. McBride KL, Varga EA, Pastore MT, Prior TW, Manickam K, Atkin JF, et al. Confirmation study of PTEN mutations among individuals with autism or developmental delays/mental retardation and macrocephaly. Autism Res. 2010;3:137–41.

    Article  PubMed  Google Scholar 

  38. Jeste SS, Varcin KJ, Hellemann GS, Gulsrud AC, Bhatt R, Kasari C, et al. Symptom profiles of autism spectrum disorder in tuberous sclerosis complex. Neurology. 2016;87:766–72.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Richards C, Jones C, Groves L, Moss J, Oliver C. Prevalence of autism spectrum disorder phenomenology in genetic disorders: a systematic review and meta-analysis. Lancet Psychiatry. 2015;2:909–16.

    Article  PubMed  Google Scholar 

  40. Feng W, Kawauchi D, Korkel-Qu H, Deng H, Serger E, Sieber L, et al. Chd7 is indispensable for mammalian brain development through activation of a neuronal differentiation programme. Nat Commun. 2017;8:14758.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Garg S, Green J, Leadbitter K, Emsley R, Lehtonen A, Evans DG, et al. Neurofibromatosis type 1 and autism spectrum disorder. Pediatrics. 2013;132:e1642–8.

    Article  PubMed  Google Scholar 

  42. Jurecka A, Zikanova M, Kmoch S, Tylki-Szymanska A. Adenylosuccinate lyase deficiency. J Inherit Metab Dis. 2015;38:231–42.

    Article  PubMed  CAS  Google Scholar 

  43. Schulze A, Bauman M, Tsai AC, Reynolds A, Roberts W, Anagnostou E, et al. Prevalence of creatine deficiency syndromes in children with nonsyndromic autism. Pediatrics. 2016;137:e20152672.

    Article  Google Scholar 

  44. Thurm A, Tierney E, Farmer C, Albert P, Joseph L, Swedo S, et al. Development, behavior, and biomarker characterization of Smith-Lemli-Opitz syndrome: an update. J Neurodev Disord. 2016;8:12.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Sztainberg Y, Zoghbi HY. Lessons learned from studying syndromic autism spectrum disorders. Nat Neurosci. 2016;19:1408–17.

    Article  PubMed  CAS  Google Scholar 

  46. Frazer KA, Murray SS, Schork NJ, Topol EJ. Human genetic variation and its contribution to complex traits. Nat Rev Genet. 2009;10:241–51.

    Article  PubMed  CAS  Google Scholar 

  47. Chaste P, Klei L, Sanders SJ, Hus V, Murtha MT, Lowe JK, et al. A genome-wide association study of autism using the simons simplex collection: Does reducing phenotypic heterogeneity in autism increase genetic homogeneity? Biol Psychiatry. 2015;77:775–84.

    Article  PubMed  Google Scholar 

  48. Wang K, Zhang H, Ma D, Bucan M, Glessner JT, Abrahams BS, et al. Common genetic variants on 5p14.1 associate with autism spectrum disorders. Nature. 2009;459:528–33.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Anney R, Klei L, Pinto D, Regan R, Conroy J, Magalhaes TR, et al. A genome-wide scan for common alleles affecting risk for autism. Hum Mol Genet. 2010;19:4072–82.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Sanders SJ, Murtha MT, Gupta AR, Murdoch JD, Raubeson MJ, Willsey AJ, et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature. 2012;485:237–41.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. De Rubeis S, He X, Goldberg AP, Poultney CS, Samocha K, Cicek AE, et al. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature. 2014;515:209–15.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Wang T, Guo H, Xiong B, Stessman HA, Wu H, Coe BP, et al. De novo genic mutations among a Chinese autism spectrum disorder cohort. Nat Commun. 2016;7:13316.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Brandler WM, Antaki D. Paternally inherited cis-regulatory structural variants are associated with autism. Science. 2018;360:327–31.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  54. Robinson EB, Koenen KC, McCormick MC, Munir K, Hallett V, Happe F, et al. Evidence that autistic traits show the same etiology in the general population and at the quantitative extremes (5%, 2.5%, and 1%). Arch Gen Psychiatry. 2011;68:1113–21.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Robinson EB, St Pourcain B, Anttila V. Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population. Nat Genet. 2016;48:552–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Klei L, Sanders SJ, Murtha MT, Hus V, Lowe JK, Willsey AJ, et al. Common genetic variants, acting additively, are a major source of risk for autism. Mol Autism. 2012;3:9.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Ruderfer DM, Hamamsy T, Lek M, Karczewski KJ, Kavanagh D, Samocha KE, et al. Patterns of genic intolerance of rare copy number variation in 59,898 human exomes. Nat Genet. 2016;48:1107–11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Leppa VM, Kravitz SN, Martin CL, Andrieux J, Le Caignec C, Martin-Coignard D, et al. Rare inherited and de novo CNVs reveal complex contributions to ASD Risk in multiplex families. Am J Hum Genet. 2016;99:540–54.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Beaudet AL. Autism: highly heritable but not inherited. Nat Med. 2007;13:534–6.

    Article  PubMed  CAS  Google Scholar 

  60. Kato T. Whole genome/exome sequencing in mood and psychotic disorders. Psychiatry Clin Neurosci. 2015;69:65–76.

    Article  PubMed  CAS  Google Scholar 

  61. Hoeffding LK, Trabjerg BB, Olsen L, Mazin W, Sparso T, Vangkilde A, et al. Risk of psychiatric disorders among individuals with the 22q11.2 deletion or duplication: a Danish nationwide, register-based study. JAMA Psychiatry. 2017;74:282–90.

    Article  PubMed  Google Scholar 

  62. 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Emanuel BS, Shaikh TH. Segmental duplications: an ‘expanding’ role in genomic instability and disease. Nat Rev Genet. 2001;2:791–800.

    Article  PubMed  CAS  Google Scholar 

  64. Guo H, Peng Y, Hu Z, Li Y, Xun G, Ou J, et al. Genome-wide copy number variation analysis in a Chinese autism spectrum disorder cohort. Sci Rep. 2017;7:44155.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Wong CC, Meaburn EL, Ronald A, Price TS, Jeffries AR, Schalkwyk LC, et al. Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits. Mol Psychiatry. 2014;19:495–503.

    Article  PubMed  CAS  Google Scholar 

  66. Loke YJ, Hannan AJ, Craig JM. The role of epigenetic change in autism spectrum disorders. Front Neurol. 2015;6:107.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Ladd-Acosta C, Hansen KD, Briem E, Fallin MD, Kaufmann WE, Feinberg AP. Common DNA methylation alterations in multiple brain regions in autism. Mol Psychiatry. 2014;19:862–71.

    Article  PubMed  CAS  Google Scholar 

  68. Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324:930–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Zhubi A, Chen Y, Dong E, Cook EH, Guidotti A, Grayson DR. Increased binding of MeCP2 to the GAD1 and RELN promoters may be mediated by an enrichment of 5-hmC in autism spectrum disorder (ASD) cerebellum. Transl Psychiatry. 2014;4:e349.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Wu YE, Parikshak NN, Belgard TG, Geschwind DH. Genome-wide, integrative analysis implicates microRNA dysregulation in autism spectrum disorder. Nat Neurosci. 2016;19:1463–76.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Yip BHK, Bai D, Mahjani B, Klei L, Pawitan Y, Hultman CM, et al. Heritable variation, with little or no maternal effect, accounts for recurrence risk to autism spectrum disorder in Sweden. Biol Psychiatry. 2018;83:589–97.

    Article  PubMed  Google Scholar 

  72. Schmidt RJ, Hansen RL, Hartiala J, Allayee H, Schmidt LC, Tancredi DJ, et al. Prenatal vitamins, one-carbon metabolism gene variants, and risk for autism. Epidemiol (Cambridge, Mass). 2011;22:476–85.

    Article  Google Scholar 

  73. Grayson DR, Guidotti A. Merging data from genetic and epigenetic approaches to better understand autistic spectrum disorder. Epigenomics. 2016;8:85–104.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Hulbert SW, Jiang YH. Monogenic mouse models of autism spectrum disorders: common mechanisms and missing links. Neuroscience. 2016;321:3–23.

    Article  PubMed  CAS  Google Scholar 

  75. Jamain S, Radyushkin K, Hammerschmidt K, Granon S, Boretius S, Varoqueaux F, et al. Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism. Proc Natl Acad Sci USA. 2008;105:1710–5.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Kazdoba TM, Leach PT, Crawley JN. Behavioral phenotypes of genetic mouse models of autism. Genes Brain Behav. 2016;15:7–26.

    Article  PubMed  CAS  Google Scholar 

  77. Katayama Y, Nishiyama M, Shoji H, Ohkawa Y, Kawamura A, Sato T, et al. CHD8 haploinsufficiency results in autistic-like phenotypes in mice. Nature. 2016;537:675–9.

    Article  PubMed  CAS  Google Scholar 

  78. Mukai J, Dhilla A, Drew LJ, Stark KL, Cao L, MacDermott AB, et al. Palmitoylation-dependent neurodevelopmental deficits in a mouse model of 22q11 microdeletion. Nat Neurosci. 2008;11:1302–10.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Mabunga DF, Gonzales EL, Kim JW, Kim KC, Shin CY. Exploring the validity of valproic acid animal model of autism. Exp Neurobiol. 2015;24:285–300.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Liu Z, Li X, Zhang JT, Cai YJ, Cheng TL, Cheng C, et al. Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2. Nature. 2016;530:98–102.

    Article  PubMed  CAS  Google Scholar 

  81. Meshalkina DA, Marina NK, Elana VK, Collier AD, Echevarria DJ, Abreu MS, et al. Zebrafish models of autism spectrum disorder. Exp Neurol. 2017;299:207–16.

    Article  PubMed  CAS  Google Scholar 

  82. Sener EF, Canatan H, Ozkul Y. Recent advances in autism spectrum disorders: applications of whole exome sequencing technology. Psychiatry Investig. 2016;13:255–64.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. O’Roak BJ, Vives L, Girirajan S, Karakoc E, Krumm N, Coe BP, et al. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature. 2012;485:246–50.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Neale BM, Kou Y, Liu L, Ma’ayan A, Samocha KE, Sabo A, et al. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature. 2012;485:242–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Codina-Sola M, Rodriguez-Santiago B, Homs A, Santoyo J, Rigau M, Aznar-Lain G, et al. Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders. Mol Autism. 2015;6:21.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Lozano R, Vino A, Lozano C, Fisher SE, Deriziotis P. A de novo FOXP1 variant in a patient with autism, intellectual disability and severe speech and language impairment. Eur J Hum Genet. 2015;23:1702–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Rk CY, Merico D, Bookman M, Howe JL, Thiruvahindrapuram B, Patel RV, et al. Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. Nat Neurosci. 2017;20:602–11.

    Article  CAS  Google Scholar 

  88. Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010;86:749–64.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Lee H, Deignan JL, Dorrani N, Strom SP, Kantarci S, Quintero-Rivera F, et al. Clinical exome sequencing for genetic identification of rare mendelian disorders. JAMA. 2014;312:1880–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Vitrac A, Cloez-Tayarani I. Induced pluripotent stem cells as a tool to study brain circuits in autism-related disorders. Stem cell Res Ther. 2018;9:226.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Funding

X.L. was supported in part by the National Key Research and Development Program of China (No. 2016YFC0900400), the National Natural Science Foundation of China (31771395, 31571518), and the International Collaboration Program of Science Technology Department of Zhejiang Province (2016C34004). The authors declare that they have no financial or nonfinancial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.

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Authors and Affiliations

  1. Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China

    Xi-Cheng Zhang, Xing-Sen Zhao & Xue-Kun Li

  2. Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, 310029, China

    Xi-Cheng Zhang, Xing-Sen Zhao & Xue-Kun Li

  3. School of Medicine and Health Sciences, George Washington University, Washington, DC, USA

    Li-Qi Shu

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XL, XZ, LS, and XZ wrote the manuscript.

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Zhang, XC., Shu, LQ., Zhao, XS. et al. Autism spectrum disorders: autistic phenotypes and complicated mechanisms. World J Pediatr 15, 17–25 (2019). https://doi.org/10.1007/s12519-018-0210-2

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