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image of Neurological Insights into 16p11.2- And 22q11.2-Related Disorders: A Mini-Review

Abstract

Copy Number Variations (CNVs) involving 16p11.2 or 22q11.2 are often linked to neurodevelopmental and neuropsychiatric disorders, including autism spectrum disorder, attention deficit hyperactivity disorder, cognitive impairment, epilepsy, and schizophrenia. The pathogenetic mechanisms underlying these neurological phenotypes remain incompletely understood, partly due to the multitude of genes involved and the complex gene-gene interactions at these loci. Nonetheless, recent advances in experimental technology and bioinformatics have greatly enhanced our understanding of the neurobiology of 16p11.2- and 22q11.2-related disorders. Herein, we aim to provide an updated mini-review on neurological aspects of these disease-associated CNVs, with emphasis on clinical and mechanistic insights as well as potential therapeutic implications.

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2025-01-24
2025-07-14

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References

  1. Marshall C.R. Howrigan D.P. Merico D. Thiruvahindrapuram B. Wu W. Greer D.S. Antaki D. Shetty A. Holmans P.A. Pinto D. Gujral M. Brandler W.M. Malhotra D. Wang Z. Fajarado K.V.F. Maile M.S. Ripke S. Agartz I. Albus M. Alexander M. Amin F. Atkins J. Bacanu S.A. Belliveau R.A. Jr Bergen S.E. Bertalan M. Bevilacqua E. Bigdeli T.B. Black D.W. Bruggeman R. Buccola N.G. Buckner R.L. Bulik-Sullivan B. Byerley W. Cahn W. Cai G. Cairns M.J. Campion D. Cantor R.M. Carr V.J. Carrera N. Catts S.V. Chambert K.D. Cheng W. Cloninger C.R. Cohen D. Cormican P. Craddock N. Crespo-Facorro B. Crowley J.J. Curtis D. Davidson M. Davis K.L. Degenhardt F. Del Favero J. DeLisi L.E. Dikeos D. Dinan T. Djurovic S. Donohoe G. Drapeau E. Duan J. Dudbridge F. Eichhammer P. Eriksson J. Escott-Price V. Essioux L. Fanous A.H. Farh K.H. Farrell M.S. Frank J. Franke L. Freedman R. Freimer N.B. Friedman J.I. Forstner A.J. Fromer M. Genovese G. Georgieva L. Gershon E.S. Giegling I. Giusti-Rodríguez P. Godard S. Goldstein J.I. Gratten J. de Haan L. Hamshere M.L. Hansen M. Hansen T. Haroutunian V. Hartmann A.M. Henskens F.A. Herms S. Hirschhorn J.N. Hoffmann P. Hofman A. Huang H. Ikeda M. Joa I. Kähler A.K. Kahn R.S. Kalaydjieva L. Karjalainen J. Kavanagh D. Keller M.C. Kelly B.J. Kennedy J.L. Kim Y. Knowles J.A. Konte B. Laurent C. Lee P. Lee S.H. Legge S.E. Lerer B. Levy D.L. Liang K.Y. Lieberman J. Lönnqvist J. Loughland C.M. Magnusson P.K.E. Maher B.S. Maier W. Mallet J. Mattheisen M. Mattingsdal M. McCarley R.W. McDonald C. McIntosh A.M. Meier S. Meijer C.J. Melle I. Mesholam-Gately R.I. Metspalu A. Michie P.T. Milani L. Milanova V. Mokrab Y. Morris D.W. Müller-Myhsok B. Murphy K.C. Murray R.M. Myin-Germeys I. Nenadic I. Nertney D.A. Nestadt G. Nicodemus K.K. Nisenbaum L. Nordin A. O’Callaghan E. O’Dushlaine C. Oh S.Y. Olincy A. Olsen L. O’Neill F.A. Van Os J. Pantelis C. Papadimitriou G.N. Parkhomenko E. Pato M.T. Paunio T. Perkins D.O. Pers T.H. Pietiläinen O. Pimm J. Pocklington A.J. Powell J. Price A. Pulver A.E. Purcell S.M. Quested D. Rasmussen H.B. Reichenberg A. Reimers M.A. Richards A.L. Roffman J.L. Roussos P. Ruderfer D.M. Salomaa V. Sanders A.R. Savitz A. Schall U. Schulze T.G. Schwab S.G. Scolnick E.M. Scott R.J. Seidman L.J. Shi J. Silverman J.M. Smoller J.W. Söderman E. Spencer C.C.A. Stahl E.A. Strengman E. Strohmaier J. Stroup T.S. Suvisaari J. Svrakic D.M. Szatkiewicz J.P. Thirumalai S. Tooney P.A. Veijola J. Visscher P.M. Waddington J. Walsh D. Webb B.T. Weiser M. Wildenauer D.B. Williams N.M. Williams S. Witt S.H. Wolen A.R. Wormley B.K. Wray N.R. Wu J.Q. Zai C.C. Adolfsson R. Andreassen O.A. Blackwood D.H.R. Bramon E. Buxbaum J.D. Cichon S. Collier D.A. Corvin A. Daly M.J. Darvasi A. Domenici E. Esko T. Gejman P.V. Gill M. Gurling H. Hultman C.M. Iwata N. Jablensky A.V. Jönsson E.G. Kendler K.S. Kirov G. Knight J. Levinson D.F. Li Q.S. McCarroll S.A. McQuillin A. Moran J.L. Mowry B.J. Nöthen M.M. Ophoff R.A. Owen M.J. Palotie A. Pato C.N. Petryshen T.L. Posthuma D. Rietschel M. Riley B.P. Rujescu D. Sklar P. St Clair D. Walters J.T.R. Werge T. Sullivan P.F. O’Donovan M.C. Scherer S.W. Neale B.M. Sebat J. Psychosis Endophenotypes International Consortium CNV and Schizophrenia Working Groups of the Psychiatric Genomics Consortium Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects. Nat. Genet. 2017 49 1 27 35 10.1038/ng.3725 27869829
    [Google Scholar]
  2. Montanucci L. Lewis-Smith D. Collins R.L. Niestroj L.M. Parthasarathy S. Xian J. Ganesan S. Macnee M. Brünger T. Thomas R.H. Talkowski M. Motelow J.E. Povysil G. Dhindsa R.S. Stanley K.E. Allen A.S. Goldstein D.B. Feng Y-C.A. Howrigan D.P. Abbott L.E. Tashman K. Cerrato F. Cusick C. Singh T. Heyne H. Byrnes A.E. Churchhouse C. Watts N. Solomonson M. Lal D. Gupta N. Neale B.M. Berkovic S.F. Lerche H. Lowenstein D.H. Cavalleri G.L. Cossette P. Cotsapas C. De Jonghe P. Dixon-Salazar T. Guerrini R. Hakonarson H. Heinzen E.L. Helbig I. Kwan P. Marson A.G. Petrovski S. Kamalakaran S. Sisodiya S.M. Stewart R. Weckhuysen S. Depondt C. Dlugos D.J. Scheffer I.E. Striano P. Freyer C. Krause R. May P. McKenna K. Regan B.M. Bennett C.A. Leech S.L. Leu C. Lewis-Smith D. O’Brien T.J. Todaro M. Stamberger H. Depondti C. Andrade D.M. Ali Q.Z. Sadoway T.R. Krestel H. Schaller A. Papacostas S.S. Kousiappa I. Tanteles G.A. Yiolanda C. Štěrbová K. Vlčková M. Sedláčková L. Laššuthová P. Klein K.M. Rosenow F. Reif P.S. Knake S. Neubauer B.A. Zimprich F. Feucht M. Reinthaler E. Kunz W.S. Zsurka G. Surges R. Baumgartner T.H. von Wrede R. Helbig I. Pendziwiat M. Muhle H. Rademacher A. van Baalen A. von Spiczak S. Stephani U. Afawi Z. Korczyn A.D. Kanaan M. Canavati C. Kurlemann G. Müller-Schlüter K. Kluger G. Häusler M. Blatt I. Lemke J.R. Krey I. Weber Y.G. Wolking S. Becker F. Lauxmann S. Bosselmann C. Kegele J. Hengsbach C. Rau S. Steinhoff B.J. Schulze-Bonhage A. Borggräfe I. Schankin C.J. Schubert-Bast S. Schreiber H. Mayer T. Korinthenberg R. Brockmann K. Wolff M. Kurlemann G. Dennig D. Madeleyn R. Kälviäinen R. Saarela A. Timonen O. Linnankivi T. Lehesjoki A-E. Rheims S. Lesca G. Ryvlin P. Maillard L. Valton L. Derambure P. Bartolomei F. Hirsch E. Michel V. Chassoux F. Rees M.I. Chung S-K. Pickrell W.O. Powell R.H.W. Baker M.D. Fonferko-Shadrach B. Lawthom C. Anderson J. Schneider N. Balestrini S. Zagaglia S. Braatz V. Johnson M.R. Auce P. Sills G.J. Kwan P. Baum L.W. Sham P.C. Cherny S.S. Lui C.H.T. Delanty N. Doherty C.P. Shukralla A. El-Naggar H. Widdess-Walsh P. Barišić N. Canafoglia L. Franceschetti S. Castellotti B. Granata T. Ragona F. Zara F. Iacomino M. Riva A. Madia F. Vari M.S. Salpietro V. Scala M. Mancardi M.M. Lino N. Amadori E. Giacomini T. Bisulli F. Pippucci T. Licchetta L. Minardi R. Tinuper P. Muccioli L. Mostacci B. Gambardella A. Labate A. Annesi G. Manna L. Gagliardi M. Parrini E. Mei D. Vetro A. Bianchini C. Montomoli M. Doccini V. Barba C. Hirose S. Ishii A. Suzuki T. Inoue Y. Yamakawa K. Beydoun A. Nasreddine W. Khoueiry-Zgheib N. Tumiene B. Utkus A. Sadleir L.G. King C. Caglayan S.H. Arslan M. Yapıcı Z. Topaloglu P. Kara B. Yis U. Turkdogan D. Gundogdu-Eken A. Bebek N. Uğur-İşeri S. Baykan B. Salman B. Haryanyan G. Yücesan E. Kesim Y. Özkara Ç. Tsai M-H. Ho C-J. Lin C-H. Lin K-L. Chou I-J. Poduri A. Shiedley B.R. Shain C. Noebels J.L. Goldman A. Busch R.M. Jehi L. Najm I.M. Lal D. Ferguson L. Khoury J. Glauser T.A. Clark P.O. Buono R.J. Ferraro T.N. Sperling M.R. Dlugos D.J. Lo W. Privitera M. French J.A. Schachter S. Kuzniecky R.I. Devinsky O. Hegde M. Greenberg D.A. Ellis C.A. Goldberg E. Helbig K.L. Cosico M. Vaidiswaran P. Fitch E. Newton C.R.J.C. Kariuki S.M. Wagner R.G. Owusu-Agyei S. Cole A.J. McGraw C.M. Siena S.A. Davis L. Hucks D. Faucon A. Wu D. Abou-Khalil B.W. Haas K. Taneja R.S. Helbig I. Leu C. Lal D. Epi25 Collaborative Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals. Nat. Commun. 2023 14 1 4392 10.1038/s41467‑023‑39539‑6 37474567
    [Google Scholar]
  3. Matalon N. Shani S. Weinberger R. Serur Y. Somech R. Givon U. Katz U. Levy-Shraga Y. Carmel E. Weiss B. Ben-Zeev B. Hochberg Y. Gur R.E. Gothelf D. The contribution of medical burden to 22q11.2 deletion syndrome quality of life and functioning. Genet. Med. 2023 25 10 100924 10.1016/j.gim.2023.100924 37422717
    [Google Scholar]
  4. Malhotra D. Sebat J. CNVs: harbingers of a rare variant revolution in psychiatric genetics. Cell 2012 148 6 1223 1241 10.1016/j.cell.2012.02.039 22424231
    [Google Scholar]
  5. Duarte M. Afonso J. Moreira A. Antunes D. Ferreira C. Correia H. Marques M. Sequeira S. Hyperprolinemia as a clue in the diagnosis of a patient with psychiatric manifestations. Brain Dev. 2017 39 6 539 541 10.1016/j.braindev.2017.01.008 28202261
    [Google Scholar]
  6. Bertrán M. Tagle F.P. Irarrázaval M. Psychiatric manifestations of 22q11.2 deletion syndrome: A literature review. Neurología (English Edition) 2018 33 2 121 128 10.1016/j.nrleng.2015.07.014 26410024
    [Google Scholar]
  7. Rein B. Yan Z. 16p11.2 Copy Number Variations and Neurodevelopmental Disorders. Trends Neurosci. 2020 43 11 886 901 10.1016/j.tins.2020.09.001 32993859
    [Google Scholar]
  8. Weiss L.A. Shen Y. Korn J.M. Arking D.E. Miller D.T. Fossdal R. Saemundsen E. Stefansson H. Ferreira M.A.R. Green T. Platt O.S. Ruderfer D.M. Walsh C.A. Altshuler D. Chakravarti A. Tanzi R.E. Stefansson K. Santangelo S.L. Gusella J.F. Sklar P. Wu B.L. Daly M.J. Autism Consortium Association between microdeletion and microduplication at 16p11.2 and autism. N. Engl. J. Med. 2008 358 7 667 675 10.1056/NEJMoa075974 18184952
    [Google Scholar]
  9. Vaez M. Montalbano S. Calle Sánchez X. Georgii Hellberg K.L. Dehkordi S.R. Krebs M.D. Meijsen J. Shorter J. Bybjerg-Grauholm J. Mortensen P.B. Børglum A.D. Hougaard D.M. Nordentoft M. Geschwind D.H. Buil A. Schork A.J. Helenius D. Raznahan A. Thompson W.K. Werge T. Ingason A. Børglum A.D. Hougaard D.M. Nordentoft M. Mors O. Mortensen P.B. Werge T. Grove J. Als T.D. Buil A. Rosengren A. Ingason A. Schork A.J. Helenius D. Gådin J. Zetterberg R. Appadurai V. Meijsen J. Georgii Hellberg K-L. Vilhjálmsson B.J. Pedersen C.B. Agerbo E. Christensen J. Petersen L.V. Gjørtz Pedersen M. Byberg-Grauholm J. Bækvad-Hansen M. iPSYCH Investigators Population-Based Risk of Psychiatric Disorders Associated With Recurrent Copy Number Variants. JAMA Psychiatry 2024 81 10 957 966 10.1001/jamapsychiatry.2024.1453 38922630
    [Google Scholar]
  10. Niarchou M. Chawner S.J.R.A. Doherty J.L. Maillard A.M. Jacquemont S. Chung W.K. Green-Snyder L. Bernier R.A. Goin-Kochel R.P. Hanson E. Linden D.E.J. Linden S.C. Raymond F.L. Skuse D. Hall J. Owen M.J. Bree M.B.M. Psychiatric disorders in children with 16p11.2 deletion and duplication. Transl. Psychiatry 2019 9 1 8 10.1038/s41398‑018‑0339‑8 30664628
    [Google Scholar]
  11. Hanson E. Bernier R. Porche K. Jackson F.I. Goin-Kochel R.P. Snyder L.G. Snow A.V. Wallace A.S. Campe K.L. Zhang Y. Chen Q. D’Angelo D. Moreno-De-Luca A. Orr P.T. Boomer K.B. Evans D.W. Kanne S. Berry L. Miller F.K. Olson J. Sherr E. Martin C.L. Ledbetter D.H. Spiro J.E. Chung W.K. Simons Variation in Individuals Project Consortium The cognitive and behavioral phenotype of the 16p11.2 deletion in a clinically ascertained population. Biol. Psychiatry 2015 77 9 785 793 10.1016/j.biopsych.2014.04.021 25064419
    [Google Scholar]
  12. Bertero A. Liska A. Pagani M. Parolisi R. Masferrer M.E. Gritti M. Pedrazzoli M. Galbusera A. Sarica A. Cerasa A. Buffelli M. Tonini R. Buffo A. Gross C. Pasqualetti M. Gozzi A. Autism-associated 16p11.2 microdeletion impairs prefrontal functional connectivity in mouse and human. Brain 2018 141 7 2055 2065 10.1093/brain/awy111 29722793
    [Google Scholar]
  13. Richter M. Murtaza N. Scharrenberg R. White S.H. Johanns O. Walker S. Yuen R.K.C. Schwanke B. Bedürftig B. Henis M. Scharf S. Kraus V. Dörk R. Hellmann J. Lindenmaier Z. Ellegood J. Hartung H. Kwan V. Sedlacik J. Fiehler J. Schweizer M. Lerch J.P. Hanganu-Opatz I.L. Morellini F. Scherer S.W. Singh K.K. Calderon de Anda F. Altered TAOK2 activity causes autism-related neurodevelopmental and cognitive abnormalities through RhoA signaling. Mol. Psychiatry 2019 24 9 1329 1350 10.1038/s41380‑018‑0025‑5 29467497
    [Google Scholar]
  14. Radoeva P.D. Coman I.L. Salazar C.A. Gentile K.L. Higgins A.M. Middleton F.A. Antshel K.M. Fremont W. Shprintzen R.J. Morrow B.E. Kates W.R. Association between autism spectrum disorder in individuals with velocardiofacial (22q11.2 deletion) syndrome and PRODH and COMT genotypes. Psychiatr. Genet. 2014 24 6 269 272 10.1097/YPG.0000000000000062 25325218
    [Google Scholar]
  15. Olsen L. Sparsø T. Weinsheimer S.M. Dos Santos M.B.Q. Mazin W. Rosengren A. Sanchez X.C. Hoeffding L.K. Schmock H. Baekvad-Hansen M. Bybjerg-Grauholm J. Daly M.J. Neale B.M. Pedersen M.G. Agerbo E. Mors O. Børglum A. Nordentoft M. Hougaard D.M. Mortensen P.B. Geschwind D.H. Pedersen C. Thompson W.K. Werge T. Prevalence of rearrangements in the 22q11.2 region and population-based risk of neuropsychiatric and developmental disorders in a Danish population: a case-cohort study. Lancet Psychiatry 2018 5 7 573 580 10.1016/S2215‑0366(18)30168‑8 29886042
    [Google Scholar]
  16. Glessner J.T. Khan M.E. Chang X. Liu Y. Otieno F.G. Lemma M. Slaby I. Hain H. Mentch F. Li J. Kao C. Sleiman P.M.A. March M.E. Connolly J. Hakonarson H. Rare recurrent copy number variations in metabotropic glutamate receptor interacting genes in children with neurodevelopmental disorders. J. Neurodev. Disord. 2023 15 1 14 10.1186/s11689‑023‑09483‑z 37120522
    [Google Scholar]
  17. Bearden C.E. van Erp T.G.M. Dutton R.A. Lee A.D. Simon T.J. Cannon T.D. Emanuel B.S. McDonald-McGinn D. Zackai E.H. Thompson P.M. Alterations in midline cortical thickness and gyrification patterns mapped in children with 22q11.2 deletions. Cereb. Cortex 2009 19 1 115 126 10.1093/cercor/bhn064 18483006
    [Google Scholar]
  18. Duyzend M.H. Eichler E.E. Genotype-first analysis of the 16p11.2 deletion defines a new type of “autism”. Biol. Psychiatry 2015 77 9 769 771 10.1016/j.biopsych.2015.02.032 25843334
    [Google Scholar]
  19. Vysotskiy M. Zhong X. Miller-Fleming T.W. Zhou D. Cox N.J. Weiss L.A. Autism Working Group of the Psychiatric Genomics Consortium^ Bipolar Disorder Working Group of the Psychiatric Genomics Consortium^ Schizophrenia Working Group of the Psychiatric Genomics Consortium^ Integration of genetic, transcriptomic, and clinical data provides insight into 16p11.2 and 22q11.2 CNV genes. Genome Med. 2021 13 1 172 10.1186/s13073‑021‑00972‑1 34715901
    [Google Scholar]
  20. Bayat M. Bayat A. Neurological manifestation of 22q11.2 deletion syndrome. Neurol. Sci. 2022 43 3 1695 1700 10.1007/s10072‑021‑05825‑8 35039989
    [Google Scholar]
  21. de Koning M.B. van Duin E.D.A. Boot E. Bloemen O.J.N. Bakker J.A. Abel K.M. van Amelsvoort T.A.M.J. PRODH rs450046 and proline x COMT Val158Met interaction effects on intelligence and startle in adults with 22q11 deletion syndrome. Psychopharmacology (Berl.) 2015 232 17 3111 3122 10.1007/s00213‑015‑3971‑5 26068888
    [Google Scholar]
  22. Moufawad El Achkar C. Rosen A. Kessler S.K. Steinman K.J. Spence S.J. Ramocki M. Marco E.J. Green Snyder L. Spiro J.E. Chung W.K. Annapurna P. Sherr E.H. Clinical Characteristics of Seizures and Epilepsy in Individuals With Recurrent Deletions and Duplications in the 16p11.2 Region. Neurol. Genet. 2022 8 5 e200018 10.1212/NXG.0000000000200018 36531974
    [Google Scholar]
  23. Stevelink R. Campbell C. Chen S. Abou-Khalil B. Adesoji O.M. Afawi Z. Amadori E. Anderson A. Anderson J. Andrade D.M. Annesi G. Auce P. Avbersek A. Bahlo M. Baker M.D. Balagura G. Balestrini S. Barba C. Barboza K. Bartolomei F. Bast T. Baum L. Baumgartner T. Baykan B. Bebek N. Becker A.J. Becker F. Bennett C.A. Berghuis B. Berkovic S.F. Beydoun A. Bianchini C. Bisulli F. Blatt I. Bobbili D.R. Borggraefe I. Bosselmann C. Braatz V. Bradfield J.P. Brockmann K. Brody L.C. Buono R.J. Busch R.M. Caglayan H. Campbell E. Canafoglia L. Canavati C. Cascino G.D. Castellotti B. Catarino C.B. Cavalleri G.L. Cerrato F. Chassoux F. Cherny S.S. Cheung C-L. Chinthapalli K. Chou I-J. Chung S-K. Churchhouse C. Clark P.O. Cole A.J. Compston A. Coppola A. Cosico M. Cossette P. Craig J.J. Cusick C. Daly M.J. Davis L.K. de Haan G-J. Delanty N. Depondt C. Derambure P. Devinsky O. Di Vito L. Dlugos D.J. Doccini V. Doherty C.P. El-Naggar H. Elger C.E. Ellis C.A. Eriksson J.G. Faucon A. Feng Y-C.A. Ferguson L. Ferraro T.N. Ferri L. Feucht M. Fitzgerald M. Fonferko-Shadrach B. Fortunato F. Franceschetti S. Franke A. French J.A. Freri E. Gagliardi M. Gambardella A. Geller E.B. Giangregorio T. Gjerstad L. Glauser T. Goldberg E. Goldman A. Granata T. Greenberg D.A. Guerrini R. Gupta N. Haas K.F. Hakonarson H. Hallmann K. Hassanin E. Hegde M. Heinzen E.L. Helbig I. Hengsbach C. Heyne H.O. Hirose S. Hirsch E. Hjalgrim H. Howrigan D.P. Hucks D. Hung P-C. Iacomino M. Imbach L.L. Inoue Y. Ishii A. Jamnadas-Khoda J. Jehi L. Johnson M.R. Kälviäinen R. Kamatani Y. Kanaan M. Kanai M. Kantanen A-M. Kara B. Kariuki S.M. Kasperavičiūte D. Kasteleijn-Nolst Trenite D. Kato M. Kegele J. Kesim Y. Khoueiry-Zgheib N. King C. Kirsch H.E. Klein K.M. Kluger G. Knake S. Knowlton R.C. Koeleman B.P.C. Korczyn A.D. Koupparis A. Kousiappa I. Krause R. Krenn M. Krestel H. Krey I. Kunz W.S. Kurki M.I. Kurlemann G. Kuzniecky R. Kwan P. Labate A. Lacey A. Lal D. Landoulsi Z. Lau Y-L. Lauxmann S. Leech S.L. Lehesjoki A-E. Lemke J.R. Lerche H. Lesca G. Leu C. Lewin N. Lewis-Smith D. Li G.H-Y. Li Q.S. Licchetta L. Lin K-L. Lindhout D. Linnankivi T. Lopes-Cendes I. Lowenstein D.H. Lui C.H.T. Madia F. Magnusson S. Marson A.G. May P. McGraw C.M. Mei D. Mills J.L. Minardi R. Mirza N. Møller R.S. Molloy A.M. Montomoli M. Mostacci B. Muccioli L. Muhle H. Müller-Schlüter K. Najm I.M. Nasreddine W. Neale B.M. Neubauer B. Newton C.R.J.C. Nöthen M.M. Nothnagel M. Nürnberg P. O’Brien T.J. Okada Y. Ólafsson E. Oliver K.L. Özkara Ç. Palotie A. Pangilinan F. Papacostas S.S. Parrini E. Pato C.N. Pato M.T. Pendziwiat M. Petrovski S. Pickrell W.O. Pinsky R. Pippucci T. Poduri A. Pondrelli F. Powell R.H.W. Privitera M. Rademacher A. Radtke R. Ragona F. Rau S. Rees M.I. Regan B.M. Reif P.S. Rhelms S. Riva A. Rosenow F. Ryvlin P. Saarela A. Sadleir L.G. Sander J.W. Sander T. Scala M. Scattergood T. Schachter S.C. Schankin C.J. Scheffer I.E. Schmitz B. Schoch S. Schubert-Bast S. Schulze-Bonhage A. Scudieri P. Sham P. Sheidley B.R. Shih J.J. Sills G.J. Sisodiya S.M. Smith M.C. Smith P.E. Sonsma A.C.M. Speed D. Sperling M.R. Stefansson H. Stefansson K. Steinhoff B.J. Stephani U. Stewart W.C. Stipa C. Striano P. Stroink H. Strzelczyk A. Surges R. Suzuki T. Tan K.M. Taneja R.S. Tanteles G.A. Taubøll E. Thio L.L. Thomas G.N. Thomas R.H. Timonen O. Tinuper P. Todaro M. Topaloğlu P. Tozzi R. Tsai M-H. Tumiene B. Turkdogan D. Unnsteinsdóttir U. Utkus A. Vaidiswaran P. Valton L. van Baalen A. Vetro A. Vining E.P.G. Visscher F. von Brauchitsch S. von Wrede R. Wagner R.G. Weber Y.G. Weckhuysen S. Weisenberg J. Weller M. Widdess-Walsh P. Wolff M. Wolking S. Wu D. Yamakawa K. Yang W. Yapıcı Z. Yücesan E. Zagaglia S. Zahnert F. Zara F. Zhou W. Zimprich F. Zsurka G. Zulfiqar Ali Q. GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture. Nat. Genet. 2023 55 9 1471 1482 10.1038/s41588‑023‑01485‑w 37653029
    [Google Scholar]
  24. Abou-Khalil B. Auce P. Avbersek A. Bahlo M. Balding D.J. Bast T. Baum L. Becker A.J. Becker F. Berghuis B. Berkovic S.F. Boysen K.E. Bradfield J.P. Brody L.C. Buono R.J. Campbell E. Cascino G.D. Catarino C.B. Cavalleri G.L. Cherny S.S. Chinthapalli K. Coffey A.J. Compston A. Coppola A. Cossette P. Craig J.J. de Haan G-J. De Jonghe P. de Kovel C.G.F. Delanty N. Depondt C. Devinsky O. Dlugos D.J. Doherty C.P. Elger C.E. Eriksson J.G. Ferraro T.N. Feucht M. Francis B. Franke A. French J.A. Freytag S. Gaus V. Geller E.B. Gieger C. Glauser T. Glynn S. Goldstein D.B. Gui H. Guo Y. Haas K.F. Hakonarson H. Hallmann K. Haut S. Heinzen E.L. Helbig I. Hengsbach C. Hjalgrim H. Iacomino M. Ingason A. Jamnadas-Khoda J. Johnson M.R. Kälviäinen R. Kantanen A-M. Kasperavičiūte D. Kasteleijn-Nolst Trenite D. Kirsch H.E. Knowlton R.C. Koeleman B.P.C. Krause R. Krenn M. Kunz W.S. Kuzniecky R. Kwan P. Lal D. Lau Y-L. Lehesjoki A-E. Lerche H. Leu C. Lieb W. Lindhout D. Lo W.D. Lopes-Cendes I. Lowenstein D.H. Malovini A. Marson A.G. Mayer T. McCormack M. Mills J.L. Mirza N. Moerzinger M. Møller R.S. Molloy A.M. Muhle H. Newton M. Ng P-W. Nöthen M.M. Nürnberg P. O’Brien T.J. Oliver K.L. Palotie A. Pangilinan F. Peter S. Petrovski S. Poduri A. Privitera M. Radtke R. Rau S. Reif P.S. Reinthaler E.M. Rosenow F. Sander J.W. Sander T. Scattergood T. Schachter S.C. Schankin C.J. Scheffer I.E. Schmitz B. Schoch S. Sham P.C. Shih J.J. Sills G.J. Sisodiya S.M. Slattery L. Smith A. Smith D.F. Smith M.C. Smith P.E. Sonsma A.C.M. Speed D. Sperling M.R. Steinhoff B.J. Stephani U. Stevelink R. Strauch K. Striano P. Stroink H. Surges R. Tan K.M. Thio L.L. Thomas G.N. Todaro M. Tozzi R. Vari M.S. Vining E.P.G. Visscher F. von Spiczak S. Walley N.M. Weber Y.G. Wei Z. Weisenberg J. Whelan C.D. Widdess-Walsh P. Wolff M. Wolking S. Yang W. Zara F. Zimprich F. Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies. Nat. Commun. 2018 9 1 5269 10.1038/s41467‑018‑07524‑z 30531953
    [Google Scholar]
  25. Kretz P.F. Wagner C. Mikhaleva A. Montillot C. Hugel S. Morella I. Kannan M. Fischer M.C. Milhau M. Yalcin I. Brambilla R. Selloum M. Herault Y. Reymond A. Collins S.C. Yalcin B. Dissecting the autism-associated 16p11.2 locus identifies multiple drivers in neuroanatomical phenotypes and unveils a male-specific role for the major vault protein. Genome Biol. 2023 24 1 261 10.1186/s13059‑023‑03092‑8 37968726
    [Google Scholar]
  26. AlKalaf H.Y. AlHashem A.M. AlSaleh N.S. AlJohar N.M. Abo Thneen A.M. ElGhezal H.M. Bouhjar I.B. Tlili-Graiess K. Sahari A.H. Tabarki B.M. Epilepsy, neuropsychiatric phenotypes, neuroimaging findings, and genotype-neurophenotype correlation in 22q11.2 deletion syndrome. Neurosciences 2020 25 4 287 291 10.17712/nsj.2020.4.20200045 33130809
    [Google Scholar]
  27. Wither R.G. Borlot F. MacDonald A. Butcher N.J. Chow E.W.C. Bassett A.S. Andrade D.M. 22q11.2 deletion syndrome lowers seizure threshold in adult patients without epilepsy. Epilepsia 2017 58 6 1095 1101 10.1111/epi.13748 28448680
    [Google Scholar]
  28. Mudigoudar B. Nune S. Fulton S. Dayyat E. Wheless J.W. Epilepsy in 22q11.2 Deletion Syndrome: A Case Series and Literature Review. Pediatr. Neurol. 2017 76 86 90 10.1016/j.pediatrneurol.2017.08.011 28969878
    [Google Scholar]
  29. Levinson D.F. Duan J. Oh S. Wang K. Sanders A.R. Shi J. Zhang N. Mowry B.J. Olincy A. Amin F. Cloninger C.R. Silverman J.M. Buccola N.G. Byerley W.F. Black D.W. Kendler K.S. Freedman R. Dudbridge F. Pe’er I. Hakonarson H. Bergen S.E. Fanous A.H. Holmans P.A. Gejman P.V. Copy number variants in schizophrenia: confirmation of five previous findings and new evidence for 3q29 microdeletions and VIPR2 duplications. Am. J. Psychiatry 2011 168 3 302 316 10.1176/appi.ajp.2010.10060876 21285140
    [Google Scholar]
  30. Singh T. Poterba T. Curtis D. Akil H. Al Eissa M. Barchas J.D. Bass N. Bigdeli T.B. Breen G. Bromet E.J. Buckley P.F. Bunney W.E. Bybjerg-Grauholm J. Byerley W.F. Chapman S.B. Chen W.J. Churchhouse C. Craddock N. Cusick C.M. DeLisi L. Dodge S. Escamilla M.A. Eskelinen S. Fanous A.H. Faraone S.V. Fiorentino A. Francioli L. Gabriel S.B. Gage D. Gagliano Taliun S.A. Ganna A. Genovese G. Glahn D.C. Grove J. Hall M.H. Hämäläinen E. Heyne H.O. Holi M. Hougaard D.M. Howrigan D.P. Huang H. Hwu H.G. Kahn R.S. Kang H.M. Karczewski K.J. Kirov G. Knowles J.A. Lee F.S. Lehrer D.S. Lescai F. Malaspina D. Marder S.R. McCarroll S.A. McIntosh A.M. Medeiros H. Milani L. Morley C.P. Morris D.W. Mortensen P.B. Myers R.M. Nordentoft M. O’Brien N.L. Olivares A.M. Ongur D. Ouwehand W.H. Palmer D.S. Paunio T. Quested D. Rapaport M.H. Rees E. Rollins B. Satterstrom F.K. Schatzberg A. Scolnick E. Scott L.J. Sharp S.I. Sklar P. Smoller J.W. Sobell J.L. Solomonson M. Stahl E.A. Stevens C.R. Suvisaari J. Tiao G. Watson S.J. Watts N.A. Blackwood D.H. Børglum A.D. Cohen B.M. Corvin A.P. Esko T. Freimer N.B. Glatt S.J. Hultman C.M. McQuillin A. Palotie A. Pato C.N. Pato M.T. Pulver A.E. St Clair D. Tsuang M.T. Vawter M.P. Walters J.T. Werge T.M. Ophoff R.A. Sullivan P.F. Owen M.J. Boehnke M. O’Donovan M.C. Neale B.M. Daly M.J. Rare coding variants in ten genes confer substantial risk for schizophrenia. Nature 2022 604 7906 509 516 10.1038/s41586‑022‑04556‑w 35396579
    [Google Scholar]
  31. Tang S.X. Gur R.E. Longitudinal perspectives on the psychosis spectrum in 22q11.2 deletion syndrome. Am. J. Med. Genet. A. 2018 176 10 2192 2202 10.1002/ajmg.a.38500 29048724
    [Google Scholar]
  32. Brownstein C.A. Douard E. Mollon J. Smith R. Hojlo M.A. Das A. Goldman M. Garvey E. Cabral K. Li J. Bowen J. Rao A.S. Genetti C. Carroll D. Knowles E.E.M. Deaso E. Agrawal P.B. Beggs A.H. D’Angelo E. Almasy L. Alexander-Bloch A. Saci Z. Moreau C.A. Huguet G. Deo A.J. Jacquemont S. Glahn D.C. Gonzalez-Heydrich J. Similar rates of deleterious copy number variants in early-onset psychosis and autism spectrum disorder. Am. J. Psychiatry 2022 179 11 853 861 10.1176/appi.ajp.21111175 36000218
    [Google Scholar]
  33. Rees E. Kendall K. Pardiñas A.F. Legge S.E. Pocklington A. Escott-Price V. MacCabe J.H. Collier D.A. Holmans P. O’Donovan M.C. Owen M.J. Walters J.T.R. Kirov G. Analysis of intellectual disability copy number variants for association with schizophrenia. JAMA Psychiatry 2016 73 9 963 969 10.1001/jamapsychiatry.2016.1831 27602560
    [Google Scholar]
  34. Rees E. Kirov G. Sanders A. Walters J.T.R. Chambert K.D. Shi J. Szatkiewicz J. O’Dushlaine C. Richards A.L. Green E.K. Jones I. Davies G. Legge S.E. Moran J.L. Pato C. Pato M. Genovese G. Levinson D. Duan J. Moy W. Göring H.H.H. Morris D. Cormican P. Kendler K.S. O’Neill F.A. Riley B. Gill M. Corvin A. Craddock N. Sklar P. Hultman C. Sullivan P.F. Gejman P.V. McCarroll S.A. O’Donovan M.C. Owen M.J. Evidence that duplications of 22q11.2 protect against schizophrenia. Mol. Psychiatry 2014 19 1 37 40 10.1038/mp.2013.156 24217254
    [Google Scholar]
  35. Khan T.A. Revah O. Gordon A. Yoon S.J. Krawisz A.K. Goold C. Sun Y. Kim C.H. Tian Y. Li M.Y. Schaepe J.M. Ikeda K. Amin N.D. Sakai N. Yazawa M. Kushan L. Nishino S. Porteus M.H. Rapoport J.L. Bernstein J.A. O’Hara R. Bearden C.E. Hallmayer J.F. Huguenard J.R. Geschwind D.H. Dolmetsch R.E. Paşca S.P. Neuronal defects in a human cellular model of 22q11.2 deletion syndrome. Nat. Med. 2020 26 12 1888 1898 10.1038/s41591‑020‑1043‑9 32989314
    [Google Scholar]
  36. Marinaro F. Marzi M.J. Hoffmann N. Amin H. Pelizzoli R. Niola F. Nicassio F. De Pietri Tonelli D. MicroRNA‐independent functions of DGCR8 are essential for neocortical development and TBR1 expression. EMBO Rep. 2017 18 4 603 618 10.15252/embr.201642800 28232627
    [Google Scholar]
  37. Paronett E.M. Meechan D.W. Karpinski B.A. LaMantia A.S. Maynard T.M. Ranbp1, deleted in digeorge/22q11.2 deletion syndrome, is a microcephaly gene that selectively disrupts layer 2/3 cortical projection neuron generation. Cereb. Cortex 2015 25 10 3977 3993 10.1093/cercor/bhu285 25452572
    [Google Scholar]
  38. Molinard-Chenu A. Dayer A. The candidate schizophrenia risk gene DGCR2 regulates early steps of corticogenesis. Biol. Psychiatry 2018 83 8 692 706 10.1016/j.biopsych.2017.11.015 29305086
    [Google Scholar]
  39. Neuhaus E. Hattingen E. Breuer S. Steidl E. Polomac N. Rosenow F. Rüber T. Herrmann E. Ecker C. Kushan L. Lin A. Vajdi A. Bearden C.E. Jurcoane A. Heterotopia in individuals with 22q11.2 deletion syndrome. AJNR Am. J. Neuroradiol. 2021 42 11 2070 2076 10.3174/ajnr.A7283 34620586
    [Google Scholar]
  40. Schleifer C.H. O’Hora K.P. Fung H. Xu J. Robinson T.A. Wu A.S. Kushan-Wells L. Lin A. Ching C.R.K. Bearden C.E. Effects of gene dosage and development on subcortical nuclei volumes in individuals with 22q11.2 copy number variations. Neuropsychopharmacology 2024 49 6 1024 1032 10.1038/s41386‑024‑01832‑3 38431758
    [Google Scholar]
  41. Modenato C. Martin-Brevet S. Moreau C.A. Rodriguez-Herreros B. Kumar K. Draganski B. Sønderby I.E. Jacquemont S. Lessons Learned From Neuroimaging Studies of Copy Number Variants: A Systematic Review. Biol. Psychiatry 2021 90 9 596 610 10.1016/j.biopsych.2021.05.028 34509290
    [Google Scholar]
  42. Martin-Brevet S. Rodríguez-Herreros B. Nielsen J.A. Moreau C. Modenato C. Maillard A.M. Pain A. Richetin S. Jønch A.E. Qureshi A.Y. Zürcher N.R. Conus P. Chung W.K. Sherr E.H. Spiro J.E. Kherif F. Beckmann J.S. Hadjikhani N. Reymond A. Buckner R.L. Draganski B. Jacquemont S. Addor M-C. Andrieux J. Arveiler B. Baujat G. Sloan-Béna F. Belfiore M. Bonneau D. Bouquillon S. Boute O. Brusco A. Busa T. Caberg J-H. Campion D. Colombert V. Cordier M-P. David A. Debray F-G. Delrue M-A. Doco-Fenzy M. Dunkhase-Heinl U. Edery P. Fagerberg C. Faivre L. Forzano F. Genevieve D. Gérard M. Giachino D. Guichet A. Guillin O. Héron D. Isidor B. Jacquette A. Jaillard S. Journel H. Keren B. Lacombe D. Lebon S. Le Caignec C. Lemaître M-P. Lespinasse J. Mathieu-Dramart M. Mercier S. Mignot C. Missirian C. Petit F. Pilekær Sørensen K. Pinson L. Plessis G. Prieur F. Rooryck-Thambo C. Rossi M. Sanlaville D. Schlott Kristiansen B. Schluth-Bolard C. Till M. Van Haelst M. Van Maldergem L. Alupay H. Aaronson B. Ackerman S. Ankenman K. Anwar A. Atwell C. Bowe A. Beaudet A.L. Benedetti M. Berg J. Berman J. Berry L.N. Bibb A.L. Blaskey L. Brennan J. Brewton C.M. Buckner R. Bukshpun P. Burko J. Cali P. Cerban B. Chang Y. Cheong M. Chow V. Chu Z. Chudnovskaya D. Cornew L. Dale C. Dell J. Dempsey A.G. Deschamps T. Earl R. Edgar J. Elgin J. Olson J.E. Evans Y.L. Findlay A. Fischbach G.D. Fisk C. Fregeau B. Gaetz B. Gaetz L. Garza S. Gerdts J. Glenn O. Gobuty S.E. Golembski R. Greenup M. Heiken K. Hines K. Hinkley L. Jackson F.I. Jenkins J. III Jeremy R.J. Johnson K. Kanne S.M. Kessler S. Khan S.Y. Ku M. Kuschner E. Laakman A.L. Lam P. Lasala M.W. Lee H. LaGuerre K. Levy S. Cavanagh A.L. Llorens A.V. Campe K.L. Luks T.L. Marco E.J. Martin S. Martin A.J. Marzano G. Masson C. McGovern K.E. McNally Keehn R. Miller D.T. Miller F.K. Moss T.J. Murray R. Nagarajan S.S. Nowell K.P. Owen J. Paal A.M. Packer A. Page P.Z. Paul B.M. Peters A. Peterson D. Poduri A. Pojman N.J. Porche K. Proud M.B. Qasmieh S. Ramocki M.B. Reilly B. Roberts T.P.L. Shaw D. Sinha T. Smith-Packard B. Gallagher A.S. Swarnakar V. Thieu T. Triantafallou C. Vaughan R. Wakahiro M. Wallace A. Ward T. Wenegrat J. Wolken A. Quantifying the effects of 16p11.2 copy number variants on brain structure: A multisite genetic-first study. Biol. Psychiatry 2018 84 4 253 264 10.1016/j.biopsych.2018.02.1176 29778275
    [Google Scholar]
  43. Kundu S. Sair H. Sherr E.H. Mukherjee P. Rohde G.K. Discovering the gene-brain-behavior link in autism via generative machine learning. Sci. Adv. 2024 10 24 eadl5307 10.1126/sciadv.adl5307 38865470
    [Google Scholar]
  44. Qureshi A.Y. Mueller S. Snyder A.Z. Mukherjee P. Berman J.I. Roberts T.P.L. Nagarajan S.S. Spiro J.E. Chung W.K. Sherr E.H. Buckner R.L. Opposing brain differences in 16p11.2 deletion and duplication carriers. J. Neurosci. 2014 34 34 11199 11211 10.1523/JNEUROSCI.1366‑14.2014 25143601
    [Google Scholar]
  45. Urresti J. Zhang P. Moran-Losada P. Yu N.K. Negraes P.D. Trujillo C.A. Antaki D. Amar M. Chau K. Pramod A.B. Diedrich J. Tejwani L. Romero S. Sebat J. Yates J.R. III Muotri A.R. Iakoucheva L.M. Cortical organoids model early brain development disrupted by 16p11.2 copy number variants in autism. Mol. Psychiatry 2021 26 12 7560 7580 10.1038/s41380‑021‑01243‑6 34433918
    [Google Scholar]
  46. Horev G. Ellegood J. Lerch J.P. Son Y.E.E. Muthuswamy L. Vogel H. Krieger A.M. Buja A. Henkelman R.M. Wigler M. Mills A.A. Dosage-dependent phenotypes in models of 16p11.2 lesions found in autism. Proc. Natl. Acad. Sci. USA 2011 108 41 17076 17081 10.1073/pnas.1114042108 21969575
    [Google Scholar]
  47. Golzio C. Willer J. Talkowski M.E. Oh E.C. Taniguchi Y. Jacquemont S. Reymond A. Sun M. Sawa A. Gusella J.F. Kamiya A. Beckmann J.S. Katsanis N. KCTD13 is a major driver of mirrored neuroanatomical phenotypes of the 16p11.2 copy number variant. Nature 2012 485 7398 363 367 10.1038/nature11091 22596160
    [Google Scholar]
  48. Arbogast T. Razaz P. Ellegood J. McKinstry S.U. Erdin S. Currall B. Aneichyk T. Lerch J.P. Qiu L.R. Rodriguiz R.M. Henkelman R.M. Talkowski M.E. Wetsel W.C. Golzio C. Katsanis N. Kctd13-deficient mice display short-term memory impairment and sex-dependent genetic interactions. Hum. Mol. Genet. 2019 28 9 1474 1486 10.1093/hmg/ddy436 30590535
    [Google Scholar]
  49. Escamilla C.O. Filonova I. Walker A.K. Xuan Z.X. Holehonnur R. Espinosa F. Liu S. Thyme S.B. López-García I.A. Mendoza D.B. Usui N. Ellegood J. Eisch A.J. Konopka G. Lerch J.P. Schier A.F. Speed H.E. Powell C.M. Kctd13 deletion reduces synaptic transmission via increased RhoA. Nature 2017 551 7679 227 231 10.1038/nature24470 29088697
    [Google Scholar]
  50. Scharrenberg R. Richter M. Johanns O. Meka D.P. Rücker T. Murtaza N. Lindenmaier Z. Ellegood J. Naumann A. Zhao B. Schwanke B. Sedlacik J. Fiehler J. Hanganu-Opatz I.L. Lerch J.P. Singh K.K. de Anda F.C. TAOK2 rescues autism-linked developmental deficits in a 16p11.2 microdeletion mouse model. Mol. Psychiatry 2022 27 11 4707 4721 10.1038/s41380‑022‑01785‑3 36123424
    [Google Scholar]
  51. Flore G. Cioffi S. Bilio M. Illingworth E. Cortical Development Requires Mesodermal Expression of Tbx1, a Gene Haploinsufficient in 22q11.2 Deletion Syndrome. Cereb. Cortex 2017 27 3 2210 2225 27005988
    [Google Scholar]
  52. Hiramoto T. Sumiyoshi A. Yamauchi T. Tanigaki K. Shi Q. Kang G. Ryoke R. Nonaka H. Enomoto S. Izumi T. Bhat M.A. Kawashima R. Hiroi N. Tbx1, a gene encoded in 22q11.2 copy number variant, is a link between alterations in fimbria myelination and cognitive speed in mice. Mol. Psychiatry 2022 27 2 929 938 10.1038/s41380‑021‑01318‑4 34737458
    [Google Scholar]
  53. Paylor R. Glaser B. Mupo A. Ataliotis P. Spencer C. Sobotka A. Sparks C. Choi C.H. Oghalai J. Curran S. Murphy K.C. Monks S. Williams N. O’Donovan M.C. Owen M.J. Scambler P.J. Lindsay E. Tbx1 haploinsufficiency is linked to behavioral disorders in mice and humans: Implications for 22q11 deletion syndrome. Proc. Natl. Acad. Sci. USA 2006 103 20 7729 7734 10.1073/pnas.0600206103 16684884
    [Google Scholar]
  54. Iyer J. Singh M.D. Jensen M. Patel P. Pizzo L. Huber E. Koerselman H. Weiner A.T. Lepanto P. Vadodaria K. Kubina A. Wang Q. Talbert A. Yennawar S. Badano J. Manak J.R. Rolls M.M. Krishnan A. Girirajan S. Pervasive genetic interactions modulate neurodevelopmental defects of the autism-associated 16p11.2 deletion in Drosophila melanogaster. Nat. Commun. 2018 9 1 2548 10.1038/s41467‑018‑04882‑6 29959322
    [Google Scholar]
  55. Campbell P.D. Lee I. Thyme S. Granato M. Mitochondrial proteins encoded by the 22q11.2 neurodevelopmental locus regulate neural stem and progenitor cell proliferation. Mol. Psychiatry 2023 28 9 3769 3781 10.1038/s41380‑023‑02272‑z 37794116
    [Google Scholar]
  56. Kim J. Vanrobaeys Y. Kelvington B. Peterson Z. Baldwin E. Gaine M.E. Nickl-Jockschat T. Abel T. Dissecting 16p11.2 hemi-deletion to study sex-specific striatal phenotypes of neurodevelopmental disorders. Mol. Psychiatry 2024 29 5 1310 1321 10.1038/s41380‑024‑02411‑0 38278994
    [Google Scholar]
  57. Vysotskiy M. Weiss L.A. Autism Working Group of the Psychiatric Genomics Consortium Bipolar Disorder Working Group of the Psychiatric Genomics Consortium Schizophrenia Working Group of the Psychiatric Genomics Consortium Combinations of genes at the 16p11.2 and 22q11.2 CNVs contribute to neurobehavioral traits. PLoS Genet. 2023 19 6 e1010780 10.1371/journal.pgen.1010780 37267418
    [Google Scholar]
  58. Forrest M.P. Penzes P. Mechanisms of copy number variants in neuropsychiatric disorders: From genes to therapeutics. Curr. Opin. Neurobiol. 2023 82 102750 10.1016/j.conb.2023.102750 37515924
    [Google Scholar]
  59. Lin G.N. Corominas R. Lemmens I. Yang X. Tavernier J. Hill D.E. Vidal M. Sebat J. Iakoucheva L.M. Spatiotemporal 16p11.2 protein network implicates cortical late mid-fetal brain development and KCTD13-Cul3-RhoA pathway in psychiatric diseases. Neuron 2015 85 4 742 754 10.1016/j.neuron.2015.01.010 25695269
    [Google Scholar]
  60. Martin Lorenzo S. Nalesso V. Chevalier C. Birling M.C. Herault Y. Targeting the RHOA pathway improves learning and memory in adult Kctd13 and 16p11.2 deletion mouse models. Mol. Autism 2021 12 1 1 10.1186/s13229‑020‑00405‑7 33436060
    [Google Scholar]
  61. Kizner V. Naujock M. Fischer S. Jäger S. Reich S. Schlotthauer I. Zuckschwerdt K. Geiger T. Hildebrandt T. Lawless N. Macartney T. Dorner-Ciossek C. Gillardon F. CRISPR/Cas9-mediated Knockout of the Neuropsychiatric Risk Gene KCTD13 Causes Developmental Deficits in Human Cortical Neurons Derived from Induced Pluripotent Stem Cells. Mol. Neurobiol. 2020 57 2 616 634 10.1007/s12035‑019‑01727‑1 31402430
    [Google Scholar]
  62. Yadav S. Oses-Prieto J.A. Peters C.J. Zhou J. Pleasure S.J. Burlingame A.L. Jan L.Y. Jan Y.N. TAOK2 Kinase Mediates PSD95 Stability and Dendritic Spine Maturation through Septin7 Phosphorylation. Neuron 2017 93 2 379 393 10.1016/j.neuron.2016.12.006 28065648
    [Google Scholar]
  63. Wakatsuki S. Takahashi Y. Shibata M. Adachi N. Numakawa T. Kunugi H. Araki T. Small noncoding vault RNA modulates synapse formation by amplifying MAPK signaling. J. Cell Biol. 2021 220 2 e201911078 10.1083/jcb.201911078 33439240
    [Google Scholar]
  64. Blizinsky K.D. Diaz-Castro B. Forrest M.P. Schürmann B. Bach A.P. Martin-de-Saavedra M.D. Wang L. Csernansky J.G. Duan J. Penzes P. Reversal of dendritic phenotypes in 16p11.2 microduplication mouse model neurons by pharmacological targeting of a network hub. Proc. Natl. Acad. Sci. USA 2016 113 30 8520 8525 10.1073/pnas.1607014113 27402753
    [Google Scholar]
  65. Zhang N. Liu L. Fan N. Zhang Q. Wang W. Zheng M. Ma L. Li Y. Shi L. The requirement of SEPT2 and SEPT7 for migration and invasion in human breast cancer via MEK/ERK activation. Oncotarget 2016 7 38 61587 61600 10.18632/oncotarget.11402 27557506
    [Google Scholar]
  66. Miyazaki T. Hashimoto K. Uda A. Sakagami H. Nakamura Y. Saito S. Nishi M. Kume H. Tohgo A. Kaneko I. Kondo H. Fukunaga K. Kano M. Watanabe M. Takeshima H. Disturbance of cerebellar synaptic maturation in mutant mice lacking BSRPs, a novel brain‐specific receptor‐like protein family. FEBS Lett. 2006 580 17 4057 4064 10.1016/j.febslet.2006.06.043 16814779
    [Google Scholar]
  67. Lin W.S. Translating Genetic Discovery into a Mechanistic Understanding of Pediatric Movement Disorders: Lessons from Genetic Dystonias and Related Disorders. Adv. Genet. 2023 4 2 2200018 10.1002/ggn2.202200018 37288166
    [Google Scholar]
  68. Forrest M.P. Dos Santos M. Piguel N.H. Wang Y.Z. Hawkins N.A. Bagchi V.A. Dionisio L.E. Yoon S. Simkin D. Martin-de-Saavedra M.D. Gao R. Horan K.E. George A.L. Jr LeDoux M.S. Kearney J.A. Savas J.N. Penzes P. Rescue of neuropsychiatric phenotypes in a mouse model of 16p11.2 duplication syndrome by genetic correction of an epilepsy network hub. Nat. Commun. 2023 14 1 825 10.1038/s41467‑023‑36087‑x 36808153
    [Google Scholar]
  69. Chung W.K. Herrera F.F. Simon’s Searchlight Foundation Health supervision for children and adolescents with 16p11.2 deletion syndrome. Molecular Case Studies 2023 9 4 a006316 10.1101/mcs.a006316 38050025
    [Google Scholar]
  70. Guna A. Butcher N.J. Bassett A.S. Comparative mapping of the 22q11.2 deletion region and the potential of simple model organisms. J. Neurodev. Disord. 2015 7 1 18 10.1186/s11689‑015‑9113‑x 26137170
    [Google Scholar]
  71. Paterlini M. Zakharenko S.S. Lai W.S. Qin J. Zhang H. Mukai J. Westphal K.G.C. Olivier B. Sulzer D. Pavlidis P. Siegelbaum S.A. Karayiorgou M. Gogos J.A. Transcriptional and behavioral interaction between 22q11.2 orthologs modulates schizophrenia-related phenotypes in mice. Nat. Neurosci. 2005 8 11 1586 1594 10.1038/nn1562 16234811
    [Google Scholar]
  72. Mayneris-Perxachs J. Castells-Nobau A. Arnoriaga-Rodríguez M. Martin M. de la Vega-Correa L. Zapata C. Burokas A. Blasco G. Coll C. Escrichs A. Biarnés C. Moreno-Navarrete J.M. Puig J. Garre-Olmo J. Ramos R. Pedraza S. Brugada R. Vilanova J.C. Serena J. Gich J. Ramió-Torrentà L. Pérez-Brocal V. Moya A. Pamplona R. Sol J. Jové M. Ricart W. Portero-Otin M. Deco G. Maldonado R. Fernández-Real J.M. Microbiota alterations in proline metabolism impact depression. Cell Metab. 2022 34 5 681 701.e10 10.1016/j.cmet.2022.04.001 35508109
    [Google Scholar]
  73. Crabtree G.W. Park A.J. Gordon J.A. Gogos J.A. Cytosolic Accumulation of L-Proline Disrupts GABA-Ergic Transmission through GAD Blockade. Cell Rep. 2016 17 2 570 582 10.1016/j.celrep.2016.09.029 27705802
    [Google Scholar]
  74. Clelland C.L. Drouet V. Rilett K.C. Smeed J.A. Nadrich R.H. Rajparia A. Read L.L. Clelland J.D. Evidence that COMT genotype and proline interact on negative-symptom outcomes in schizophrenia and bipolar disorder. Transl. Psychiatry 2016 6 9 e891 10.1038/tp.2016.157 27622935
    [Google Scholar]
  75. Ren D. Luo B. Chen P. Yu L. Xiong M. Fu Z. Zhou T. Chen W.B. Fei E. DiGeorge syndrome critical region gene 2 (DGCR2), a schizophrenia risk gene, regulates dendritic spine development through cell adhesion. Cell Biosci. 2023 13 1 134 10.1186/s13578‑023‑01081‑9 37480133
    [Google Scholar]
  76. Maurer G.W. Malita A. Nagy S. Koyama T. Werge T.M. Halberg K.A. Texada M.J. Rewitz K. Analysis of genes within the schizophrenia-linked 22q11.2 deletion identifies interaction of night owl/LZTR1 and NF1 in GABAergic sleep control. PLoS Genet. 2020 16 4 e1008727 10.1371/journal.pgen.1008727 32339168
    [Google Scholar]
  77. Sundberg M. Pinson H. Smith R.S. Winden K.D. Venugopal P. Tai D.J.C. Gusella J.F. Talkowski M.E. Walsh C.A. Tegmark M. Sahin M. 16p11.2 deletion is associated with hyperactivation of human iPSC-derived dopaminergic neuron networks and is rescued by RHOA inhibition in vitro. Nat. Commun. 2021 12 1 2897 10.1038/s41467‑021‑23113‑z 34006844
    [Google Scholar]
  78. Gur R.C. Bearden C.E. Jacquemont S. Swillen A. van Amelsvoort T. van den Bree M. Vorstman J. Sebat J. Ruparel K. Gallagher R.S. McClellan E. White L. Crowley T.B. Giunta V. Kushan L. O’Hora K. Verbesselt J. Vandensande A. Vingerhoets C. van Haelst M. Hall J. Harwood J. Chawner S.J.R.A. Patel N. Palad K. Hong O. Guevara J. Martin C.O. Jizi K. Bélanger A.M. Scherer S.W. Bassett A.S. McDonald-McGinn D.M. Gur R.E. Neurocognitive profiles of 22q11.2 and 16p11.2 deletions and duplications. Mol. Psychiatry 2024 10.1038/s41380‑024‑02661‑y 39048645
    [Google Scholar]
  79. Kostic M. Raymond J.J. Freyre C.A.C. Henry B. Tumkaya T. Khlghatyan J. Dvornik J. Li J. Hsiao J.S. Cheon S.H. Chung J. Sun Y. Dolmetsch R.E. Worringer K.A. Ihry R.J. Patient Brain Organoids Identify a Link between the 16p11.2 Copy Number Variant and the RBFOX1 Gene. ACS Chem. Neurosci. 2023 14 22 3993 4012 10.1021/acschemneuro.3c00442 37903506
    [Google Scholar]
  80. Roth J.G. Muench K.L. Asokan A. Mallett V.M. Gai H. Verma Y. Weber S. Charlton C. Fowler J.L. Loh K.M. Dolmetsch R.E. Palmer T.D. 16p11.2 microdeletion imparts transcriptional alterations in human iPSC-derived models of early neural development. eLife 2020 9 e58178 10.7554/eLife.58178 33169669
    [Google Scholar]
  81. Shin D. Kim C.N. Ross J. Hennick K.M. Wu S.R. Paranjape N. Leonard R. Wang J.C. Keefe M.G. Pavlovic B.J. Donohue K.C. Moreau C. Wigdor E.M. Larson H.H. Allen D.E. Cadwell C.R. Bhaduri A. Popova G. Bearden C.E. Pollen A.A. Jacquemont S. Sanders S.J. Haussler D. Wiita A.P. Frost N.A. Sohal V.S. Nowakowski T.J. Thalamocortical organoids enable in vitro modeling of 22q11.2 microdeletion associated with neuropsychiatric disorders. Cell Stem Cell 2024 31 3 421 432.e8 10.1016/j.stem.2024.01.010 38382530
    [Google Scholar]
/content/journals/cg/10.2174/0113892029338299241211063307
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Neurological Insights into 16p11.2- And 22q11.2-Related Disorders: A Mini-Review
Bentham Science Publishers ; https://doi.org/10.2174/0113892029338299241211063307
/content/journals/cg/10.2174/0113892029338299241211063307
/content/journals/cg/10.2174/0113892029338299241211063307
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  • Article Type:     Review Article
Keywords: intellectual disability ; schizophrenia ; neuropsychiatric disorder ; neurodevelopmental disorder ; copy number variant ; Autism ; epilepsy

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