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8p21.3 deletions are rare causes of non-syndromic autism spectrum disorder

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Abstract

A de novo 0.95 Mb 8p21.3 deletion had been identified in an individual with non-syndromic autism spectrum disorder (ASD) through high-resolution copy number variant analysis. Subsequent screening of in-house and publicly available databases resulted in the identification of six additional individuals with 8p21.3 deletions. Through case-based reasoning, we conclude that 8p21.3 deletions are rare causes of non-syndromic neurodevelopmental and neuropsychiatric disorders. Based on literature data, we highlight six genes within the region of minimal overlap as potential ASD genes or genes for neuropsychiatric disorders: DMTN, EGR3, FGF17, LGI3, PHYHIP, and PPP3CC.

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References

  1. Cook EH, Scherer SW (2008) Copy-number variations associated with neuropsychiatric conditions. Nature 455:919–923. https://doi.org/10.1038/nature07458

    Article  CAS  PubMed  Google Scholar 

  2. Talkowski ME, Minikel EV, Gusella JF (2014) Autism spectrum disorder genetics: diverse genes with diverse clinical outcomes. Harv Rev Psychiatry 22:65–75. https://doi.org/10.1097/HRP.0000000000000002

    Article  PubMed  Google Scholar 

  3. Anney R, Klei L, Pinto D, Regan R, Conroy J, Magalhaes TR, Correia C, Abrahams BS, Sykes N, Pagnamenta AT, Almeida J, Bacchelli E, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bolte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Carson AR, Casallo G, Casey J, Chu SH, Cochrane L, Corsello C, Crawford EL, Crossett A, 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 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 X-Q, Lord C, Lotspeich L, Lund SC, Maestrini E, Mahoney W, Mantoulan C, Marshall CR, McConachie H, McDougle CJ, McGrath J, McMahon WM, Melhem NM, 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, Piven J, 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, Senman L, Shah N, Sheffield VC, Soorya L, Sousa I, 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, Wing K, Wittemeyer K, Wood S, Yaspan BL, Zurawiecki D, Zwaigenbaum L, Betancur C, Buxbaum JD, Cantor RM, Cook EH, Coon H, Cuccaro ML, Gallagher L, Geschwind DH, Gill M, Haines JL, Miller J, Monaco AP, Nurnberger JI, Paterson AD, Pericak-Vance MA, Schellenberg GD, Scherer SW, Sutcliffe JS, Szatmari P, Vicente AM, Vieland VJ, Wijsman EM, Devlin B, Ennis S, Hallmayer J (2010) A genome-wide scan for common alleles affecting risk for autism. Hum Mol Genet 19:4072–4082. https://doi.org/10.1093/hmg/ddq307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Yousaf A, Waltes R, Haslinger D, Klauck SM, Duketis E, Sachse M, Voran A, Biscaldi M, Schulte-Rüther M, Cichon S, Nöthen M, Ackermann J, Koch I, Freitag CM, Chiocchetti AG (2020) Quantitative genome-wide association study of six phenotypic subdomains identifies novel genome-wide significant variants in autism spectrum disorder. Transl Psychiatry 10:215. https://doi.org/10.1038/s41398-020-00906-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Scherer SW, Dawson G (2011) Risk factors for autism: translating genomic discoveries into diagnostics. Hum Genet 130:123–148. https://doi.org/10.1007/s00439-011-1037-2

    Article  PubMed  Google Scholar 

  6. Stessman HAF, Xiong B, Coe BP, Wang T, Hoekzema K, Fenckova M, Kvarnung M, Gerdts J, Trinh S, Cosemans N, Vives L, Lin J, Turner TN, Santen G, Ruivenkamp C, Kriek M, van Haeringen A, Aten E, Friend K, Liebelt J, Barnett C, Haan E, Shaw M, Gecz J, Anderlid B-M, Nordgren A, Lindstrand A, Schwartz C, Kooy RF, Vandeweyer G, Helsmoortel C, Romano C, Alberti A, Vinci M, Avola E, Giusto S, Courchesne E, Pramparo T, Pierce K, Nalabolu S, Amaral DG, Scheffer IE, Delatycki MB, Lockhart PJ, Hormozdiari F, Harich B, Castells-Nobau A, Xia K, Peeters H, Nordenskjöld M, Schenck A, Bernier RA, Eichler EE (2017) Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. Nat Genet 49:515–526. https://doi.org/10.1038/ng.3792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Coe BP, Witherspoon K, Rosenfeld JA, BWM v B, Vulto-van Silfhout AT, Bosco P, Friend KL, Baker C, Buono S, LELM V, Schuurs-Hoeijmakers JH, Hoischen A, Pfundt R, Krumm N, Carvill GL, Li D, Amaral D, Brown N, Lockhart PJ, Scheffer IE, Alberti A, Shaw M, Pettinato R, Tervo R, de Leeuw N, MRF R, Torchia BS, Peeters H, Thompson E, O’Roak BJ, Fichera M, Hehir-Kwa JY, Shendure J, Mefford HC, Haan E, Gécz J, BB a d V, Romano C, Eichler EE (2014) Refining analyses of copy number variation identifies specific genes associated with developmental delay. Nat Genet 46:1063–1071. https://doi.org/10.1038/ng.3092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Chong WW, Lo IF, Lam ST, Wang C, Luk H, Leung T, Choy K (2014) Performance of chromosomal microarray for patients with intellectual disabilities/developmental delay, autism, and multiple congenital anomalies in a Chinese cohort. Mol Cytogenet 7:34. https://doi.org/10.1186/1755-8166-7-34

    Article  PubMed  PubMed Central  Google Scholar 

  9. Izumi K, Mikesell H, Daber R, Chao G, Hutchinson AL, Spinner NB, Parikh AS (2011) 8p21 microdeletion in a patient with intellectual disability and behavioral abnormalities. Am J Med Genet Part A 155:3148–3152. https://doi.org/10.1002/ajmg.a.34317

    Article  CAS  Google Scholar 

  10. Wechsler D (2012) Wechsler Adult Intelligence Scale (4th ed.), Dutch version. Pearson, Amsterdam, the Netherlands

  11. Harrison PL, Oakland T (2015) Adaptive Behavior Assessment System (3rd ed.), Manual. Western Psychological Services, Torrance, California

  12. Lord C, Rutter M, DiLavore PC, Risi S, Gotham K, Bishop SL (2012) Autism Diagnostic Observation Schedule - Second edition (ADOS-2). Western Psychological Services, Torrance, CA

    Google Scholar 

  13. Skuse D, Warrington R, Bishop D, Chowdhury U, Lau J, Mandy W, Place M (2004) The Developmental, Dimensional and Diagnostic Interview (3di): a novel computerized assessment for autism spectrum disorders. J Am Acad Child Adolesc Psychiatry 43:548–558. https://doi.org/10.1097/00004583-200405000-00008

    Article  PubMed  Google Scholar 

  14. Constantino JN, Gruber CP (2012) Social Responsiveness Scale, Dutch manual. Hogrefe, Amsterdam, the Netherlands

  15. Achenbach TM, Rescorla LA (2003) Manual for the ASEBA adult forms and profiles. University of Vermont, Burlingtion, VT

    Google Scholar 

  16. Fagerberg L, Hallstrom BM, Oksvold P, Kampf C, Djureinovic D, Odeberg J, Habuka M, Tahmasebpoor S, Danielsson A, Edlund K, Asplund A, Sjostedt E, Lundberg E, Szigyarto CAK, Skogs M, Ottosson Takanen J, Berling H, Tegel H, Mulder J, Nilsson P, Schwenk JM, Lindskog C, Danielsson F, Mardinoglu A, Sivertsson A, Von Feilitzen K, Forsberg M, Zwahlen M, Olsson I, Navani S, Huss M, Nielsen J, Ponten F, Uhlen M (2014) Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics 13:397–406. https://doi.org/10.1074/mcp.M113.035600

    Article  CAS  PubMed  Google Scholar 

  17. Duff MO, Olson S, Wei X, Garrett SC, Osman A, Bolisetty M, Plocik A, Celniker S, Graveley BR (2015) Genome-wide identification of zero nucleotide recursive splicing in Drosophila. Nature 521:376–379. https://doi.org/10.1038/nature14475.Genome-wide

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Tabarés-Seisdedos R, Rubenstein JLR (2009) Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer. Mol Psychiatry 14:563–589. https://doi.org/10.1038/mp.2009.2

    Article  CAS  PubMed  Google Scholar 

  19. Gerber DJ, Hall D, Miyakawa T, Demars S, Gogos JA, Karayiorgou M, Tonegawa S (2003) Evidence for association of schizophrenia with genetic variation in the 8p21.3 gene, PPP3CC, encoding the calcineurin gamma subunit. Proc Natl Acad Sci 100:8993–8998. https://doi.org/10.1073/pnas.1432927100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chisholm K, Lin A, Abu-Akel A, Wood SJ (2015) The association between autism and schizophrenia spectrum disorders: a review of eight alternate models of co-occurrence. Neurosci Biobehav Rev 55:173–183. https://doi.org/10.1016/j.neubiorev.2015.04.012

    Article  PubMed  Google Scholar 

  21. Azim AC, Knoll JHM, Beggs AH, Chishti AH (1995) Isoform cloning, actin binding, and chromosomal localization of human erythroid dematin, a member of the villin superfamily. J Biol Chem 270:17407–17413. https://doi.org/10.1074/jbc.270.29.17407

    Article  CAS  PubMed  Google Scholar 

  22. Kim A, Azim A, Chishti A (1998) Alternative splicing and structure of the human erythroid dematin gene. Biochim Biophys Acta Gene Struct Expr 1398:382–386. https://doi.org/10.1016/S0167-4781(98)00078-5

    Article  CAS  Google Scholar 

  23. Cohen OS, Mccoy SY, Middleton FA, Bialosuknia S, Zhang-James Y, Liu L, Tsuang MT, Faraone SV, Glatt SJ (2012) Transcriptomic analysis of postmortem brain identifies dysregulated splicing events in novel candidate genes for schizophrenia. Schizophr Res 142:188–199. https://doi.org/10.1016/j.schres.2012.09.015

    Article  PubMed  PubMed Central  Google Scholar 

  24. Lutchman M, Kim AC, Cheng L, Whitehead IP, Oh SS, Hanspal M, Boukharov AA, Hanada T, Chishti AH (2002) Dematin interacts with the Ras-guanine nucleotide exchange factor Ras-GRF2 and modulates mitogen-activated protein kinase pathways. Eur J Biochem 269:638–649. https://doi.org/10.1046/j.0014-2956.2001.02694.x

    Article  CAS  PubMed  Google Scholar 

  25. Huguet G, Benabou M, Bourgeron T (2016) The genetics of autism spectrum disorders. In: Sassone-Corsi P, Christen Y (eds) A time for metabolism and hormones. Springer International Publishing, Cham, pp 101–129

    Chapter  Google Scholar 

  26. Pinto D, Delaby E, Merico D, Barbosa M, Merikangas A, Klei L, Thiruvahindrapuram B, Xu X, Ziman R, Wang Z, Vorstman JAS, Thompson A, Regan R, Pilorge M, Pellecchia G, Pagnamenta AT, Oliveira B, Marshall CR, Magalhaes TR, Lowe JK, Howe JL, Griswold AJ, Gilbert J, Duketis E, Dombroski BA, De Jonge MV, Cuccaro M, Crawford EL, Correia CT, Conroy J, Conceição IC, Chiocchetti AG, Casey JP, Cai G, Cabrol C, Bolshakova N, Bacchelli E, Anney R, Gallinger S, Cotterchio M, Casey G, Zwaigenbaum L, Wittemeyer K, Wing K, Wallace S, van Engeland H, Tryfon A, Thomson S, Soorya L, Rogé B, Roberts W, Poustka F, Mouga S, Minshew N, McInnes LA, McGrew SG, Lord C, Leboyer M, Le Couteur AS, Kolevzon A, Jiménez González P, Jacob S, Holt R, Guter S, Green J, Green A, Gillberg C, Fernandez BA, Duque F, Delorme R, Dawson G, Chaste P, Café C, Brennan S, Bourgeron T, Bolton PF, Bölte S, Bernier R, Baird G, Bailey AJ, Anagnostou E, Almeida J, Wijsman EM, Vieland VJ, Vicente AM, Schellenberg GD, Pericak-Vance M, Paterson AD, Parr JR, Oliveira G, Nurnberger JI, Monaco AP, Maestrini E, Klauck SM, Hakonarson H, Haines JL, Geschwind DH, Freitag CM, Folstein SE, Ennis S, Coon H, Battaglia A, Szatmari P, Sutcliffe JS, Hallmayer J, Gill M, Cook EH, Buxbaum JD, Devlin B, Gallagher L, Betancur C, Scherer SW (2014) Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. Am J Hum Genet 94:677–694. https://doi.org/10.1016/j.ajhg.2014.03.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Vorstman JAS, Parr JR, Moreno-De-Luca D, Anney RJL, Nurnberger JI Jr, Hallmayer JF (2017) Autism genetics: opportunities and challenges for clinical translation. Nat Rev Genet 18:362–376. https://doi.org/10.1038/nrg.2017.4

    Article  CAS  PubMed  Google Scholar 

  28. Gallitano AL, Tillman R, Dinu V, Geller B (2012) Family-based association study of early growth response gene 3 with child bipolar I disorder. J Affect Disord 138:387–396. https://doi.org/10.1016/j.jad.2012.01.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Nishimura Y, Takizawa R, Koike S, Kinoshita A, Satomura Y, Kawasaki S, Yamasue H, Tochigi M, Kakiuchi C, Sasaki T, Iwayama Y, Yamada K, Yoshikawa T, Kasai K (2014) Association of decreased prefrontal hemodynamic response during a verbal fluency task with EGR3 gene polymorphism in patients with schizophrenia and in healthy individuals. Neuroimage 85:527–534. https://doi.org/10.1016/j.neuroimage.2013.08.021

    Article  CAS  PubMed  Google Scholar 

  30. Gallitano-Mendel A, Izumi Y, Tokuda K, Zorumski CF, Howell MP, Muglia LJ, Wozniak DF, Milbrandt J (2007) The immediate early gene early growth response gene 3 mediates adaptation to stress and novelty. Neuroscience 148:633–643. https://doi.org/10.1016/j.neuroscience.2007.05.050

    Article  CAS  PubMed  Google Scholar 

  31. Yamada K, Gerber DJ, Iwayama Y, Ohnishi T, Ohba H, Toyota T, Aruga J, Minabe Y, Tonegawa S, Yoshikawa T (2007) Genetic analysis of the calcineurin pathway identifies members of the EGR gene family, specifically EGR3, as potential susceptibility candidates in schizophrenia. Proc Natl Acad Sci 104:2815–2820. https://doi.org/10.1073/pnas.0610765104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zhang R, Lu S, Meng L, Min Z, Tian J, Valenzuela RK, Guo T, Tian L, Zhao W, Ma J (2012) Genetic evidence for the association between the early growth response 3 (EGR3) Gene and schizophrenia. PLoS One 7:e30237. https://doi.org/10.1371/journal.pone.0030237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kyogoku C, Yanagi M, Nishimura K, Sugiyama D, Morinobu A, Fukutake M, Maeda K, Shirakawa O, Kuno T, Kumagai S (2011) Association of calcineurin A gamma subunit (PPP3CC) and early growth response 3 (EGR3) gene polymorphisms with susceptibility to schizophrenia in a Japanese population. Psychiatry Res 185:16–19. https://doi.org/10.1016/j.psychres.2009.11.003

    Article  CAS  PubMed  Google Scholar 

  34. Hoshikawa M, Ohbayashi N, Yonamine A, Konishi M, Ozaki K, Fukui S, Itoh N (1998) Structure and expression of a novel fibroblast growth factor, FGF-17, preferentially expressed in the embryonic brain. Biochem Biophys Res Commun 244:187–191. https://doi.org/10.1006/bbrc.1998.8239

    Article  CAS  PubMed  Google Scholar 

  35. Xu J, Lawshé A, MacArthur CA, Ornitz DM (1999) Genomic structure, mapping, activity and expression of fibroblast growth factor 17. Mech Dev 83:165–178. https://doi.org/10.1016/S0925-4773(99)00034-9

    Article  CAS  PubMed  Google Scholar 

  36. Ford-Perriss M, Abud H, Murphy M (2001) Fibroblast growth factors in the developing central nervous system. Clin Exp Pharmacol Physiol 28:493–503 cep3477 [pii]

    Article  CAS  Google Scholar 

  37. Scearce-Levie K, Roberson ED, Gerstein H, Cholfin JA, Mandiyan VS, Shah NM, Rubenstein JLR, Mucke L (2008) Abnormal social behaviors in mice lacking Fgf17. Genes Brain Behav 7:344–354. https://doi.org/10.1111/j.1601-183X.2007.00357.x

    Article  CAS  PubMed  Google Scholar 

  38. Rubenstein JLR (2010) Three hypotheses for developmental defects that may underlie some forms of autism spectrum disorder. Curr Opin Neurol 23:118–123. https://doi.org/10.1097/WCO.0b013e328336eb13

    Article  PubMed  Google Scholar 

  39. Nagase T, Seki N, Ishikawa K, Ohira M, Kawarabayasi Y, Ohara O, Tanaka A, Kotani H, Miyajima N, Nomura N (1996) Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain. DNA Res 3:321–329. https://doi.org/10.1093/dnares/3.5.321

    Article  CAS  PubMed  Google Scholar 

  40. Lee ZH, Kim H-H, Ahn KY, Seo KH, Kim JK, Bae CS, Kim KK (2000) Identification of a brain specific protein that associates with a Refsum disease gene product, phytanoyl-CoA alpha-hydroxylase. Mol Brain Res 75:237–247. https://doi.org/10.1016/S0169-328X(99)00304-6

    Article  CAS  PubMed  Google Scholar 

  41. Lee SE, Lee AY, Park WJ, Jun DH, Kwon NS, Baek KJ, Kim YG, Yun HY (2006) Mouse LGI3 gene: expression in brain and promoter analysis. Gene 372:8–17. https://doi.org/10.1016/j.gene.2005.09.008

    Article  CAS  PubMed  Google Scholar 

  42. Benarroch EE (2012) ADAM proteins, their ligands, and clinical implications. Neurology 78:914–920. https://doi.org/10.1212/WNL.0b013e31824c4728

    Article  PubMed  Google Scholar 

  43. Kegel L, Aunin E, Meijer D, Bermingham JR (2013) LGI proteins in the nervous system. ASN Neuro 5:167–181. https://doi.org/10.1042/AN20120095

    Article  CAS  PubMed  Google Scholar 

  44. Carlson GC (2012) Glutamate receptor dysfunction and drug targets across models of autism spectrum disorders. Pharmacol Biochem Behav 100:850–854. https://doi.org/10.1016/j.pbb.2011.02.003

    Article  CAS  PubMed  Google Scholar 

  45. Bescond M, Rahmani Z (2005) Dual-specificity tyrosine-phosphorylated and regulated kinase 1A (DYRK1A) interacts with the phytanoyl-CoA α-hydroxylase associated protein 1 (PAHX-AP1), a brain specific protein. Int J Biochem Cell Biol 37:775–783. https://doi.org/10.1016/j.biocel.2004.12.006

    Article  CAS  PubMed  Google Scholar 

  46. van Bon BWM, Coe BP, Bernier R, Green C, Gerdts J, Witherspoon K, Kleefstra T, Willemsen MH, Kumar R, Bosco P, Fichera M, Li D, Amaral D, Cristofoli F, Peeters H, Haan E, Romano C, Mefford HC, Scheffer I, Gecz J, de Vries BBA, Eichler EE (2016) Disruptive de novo mutations of DYRK1A lead to a syndromic form of autism and ID. Mol Psychiatry 21:126–132. https://doi.org/10.1038/mp.2015.5

    Article  CAS  PubMed  Google Scholar 

  47. Eastwood SL, Salih T, Harrison PJ (2005) Differential expression of calcineurin A subunit mRNA isoforms during rat hippocampal and cerebellar development. Eur J Neurosci 22:3017–3024. https://doi.org/10.1111/j.1460-9568.2005.04518.x

    Article  PubMed  Google Scholar 

  48. Xia Z, Storm DR (2005) The role of calmodulin as a signal integrator for synaptic plasticity. Nat Rev Neurosci 6:267–276. https://doi.org/10.1038/nrn1647

    Article  CAS  PubMed  Google Scholar 

  49. Horiuchi Y, Ishiguro H, Koga M, Inada T, Iwata N, Ozaki N, Ujike H, Muratake T, Someya T, Arinami T (2007) Support for association of the PPP3CC gene with schizophrenia. Mol Psychiatry 12:891–893. https://doi.org/10.1038/sj.mp.4002019

    Article  CAS  PubMed  Google Scholar 

  50. Eastwood SL, Burnet PWJ, Harrison PJ (2005) Decreased hippocampal expression of the susceptibility gene PPP3CC and other calcineurin subunits in schizophrenia. Biol Psychiatry 57:702–710. https://doi.org/10.1016/j.biopsych.2004.12.029

    Article  CAS  PubMed  Google Scholar 

  51. Mathieu F, Miot S, Etain B, El Khoury M-A, Chevalier F, Bellivier F, Leboyer M, Giros B, Tzavara ET (2008) Association between the PPP3CC gene, coding for the calcineurin gamma catalytic subunit, and bipolar disorder. Behav Brain Funct 4:2. https://doi.org/10.1186/1744-9081-4-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Zeng H, Chattarji S, Barbarosie M, Rondi-Reig L, Philpot BD, Miyakawa T, Bear MF, Tonegawa S (2001) Forebrain-specific calcineurin knockout selectively impairs bidirectional synaptic plasticity and working/episodic-like memory. Cell 107:617–629. https://doi.org/10.1016/S0092-8674(01)00585-2

    Article  CAS  PubMed  Google Scholar 

  53. Miyakawa T, Leiter LM, Gerber DJ, Gainetdinov RR, Sotnikova TD, Zeng H, Caron MG, Tonegawa S (2003) Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia. Proc Natl Acad Sci 100:8987–8992. https://doi.org/10.1073/pnas.1432926100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank the patient for participation in additional cognitive and behavioral assessment. We thank Dr. Shelagh Joss for sharing the information of her 8p21.3 patient through DECIPHER and providing additional information upon request. HP is a Senior Clinical Investigator of The Research Foundation—Flanders (FWO).

Availability of data and material

Detailed genetic and clinical data are available upon request.

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Not applicable

Funding

HP is a Senior Clinical Investigator of The Research Foundation - Flanders (FWO). This study was funded by a research grant “Opening the future” from KU Leuven to IN and JS and HP.

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Authors and Affiliations

  1. Center for Human Genetics, University Hospital Leuven, KU Leuven, O&N I Herestraat 49 - box 606, 3000, Leuven, Belgium

    Nele Cosemans, Annick Vogels, Maureen Holvoet, Koen Devriendt, Kris Van Den Bogaert & Hilde Peeters

  2. Leuven Autism Research (LAuRes), Leuven, Belgium

    Nele Cosemans, Jarymke Maljaars, Jean Steyaert, Ilse Noens & Hilde Peeters

  3. Parenting and Special Education Research Unit, KU Leuven, Leuven, Belgium

    Jarymke Maljaars & Ilse Noens

  4. Department of Neurosciences, KU Leuven, Leuven, Belgium

    Jean Steyaert

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  1. Nele Cosemans
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  9. Hilde Peeters
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Contributions

NC performed the research on 8p21.3 deletions, identified similar deletions, and reviewed possible candidate genes and wrote and submitted the manuscript. JM and IN performed the reassessment of the Leuven patients and drafted the accompanying results section. AV, MH, and KD provided clinical data on Leuven patients 2 and 3. JS recruited Leuven patient 1 in the original Leuven Autism Family Study. KVDB did microarray data interpretation for three Leuven patients. HP identified Leuven patient 1, supervised the additional data collection, and manuscript writing.

Corresponding author

Correspondence to Hilde Peeters.

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The study was approved by the Medical Ethical Committee of the University Hospital Leuven (reference number S50717).

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All patients gave written informed consent for genetic testing and study related procedures.

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All patients gave written informed consent for publication.

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The authors declare that they have no competing interests.

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Cosemans, N., Maljaars, J., Vogels, A. et al. 8p21.3 deletions are rare causes of non-syndromic autism spectrum disorder. Neurogenetics 22, 207–213 (2021). https://doi.org/10.1007/s10048-021-00635-8

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