{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:26:19Z","timestamp":1787160379744,"version":"build-2736575974"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T00:00:00Z","timestamp":1623283200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T00:00:00Z","timestamp":1623283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000866","name":"Cardiff University","doi-asserted-by":"publisher","award":["CMU Fellowship"],"award-info":[{"award-number":["CMU Fellowship"]}],"id":[{"id":"10.13039\/501100000866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000866","name":"Cardiff University","doi-asserted-by":"publisher","award":["CMU Studentship"],"award-info":[{"award-number":["CMU Studentship"]}],"id":[{"id":"10.13039\/501100000866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012107","name":"Waterloo Foundation","doi-asserted-by":"publisher","award":["TWF Changing Minds Programme"],"award-info":[{"award-number":["TWF Changing Minds Programme"]}],"id":[{"id":"10.13039\/100012107","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012107","name":"Waterloo Foundation","doi-asserted-by":"publisher","award":["TWF Changing Minds Programme."],"award-info":[{"award-number":["TWF Changing Minds Programme."]}],"id":[{"id":"10.13039\/100012107","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["DEFINE Strategic Award 100202\/Z\/12\/Z"],"award-info":[{"award-number":["DEFINE Strategic Award 100202\/Z\/12\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["DEFINE Strategic Award 100202\/Z\/12\/Z"],"award-info":[{"award-number":["DEFINE Strategic Award 100202\/Z\/12\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["DEFINE Strategic Award 100202\/Z\/12\/Z"],"award-info":[{"award-number":["DEFINE Strategic Award 100202\/Z\/12\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/ L010305\/1"],"award-info":[{"award-number":["MR\/ L010305\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["G0800509"],"award-info":[{"award-number":["G0800509"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/NO22572\/1"],"award-info":[{"award-number":["MR\/NO22572\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/L011166\/1"],"award-info":[{"award-number":["MR\/L011166\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Psychiatry"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Copy Number Variation (CNV) at the 1q21.1 locus is associated with a range of neurodevelopmental and psychiatric disorders in humans, including abnormalities in head size and motor deficits. Yet, the functional consequences of these CNVs (both deletion and duplication) on neuronal development remain unknown. To determine the impact of CNV at the 1q21.1 locus on neuronal development, we generated induced pluripotent stem cells from individuals harbouring 1q21.1 deletion or duplication and differentiated them into functional cortical neurons. We show that neurons with 1q21.1 deletion or duplication display reciprocal phenotype with respect to proliferation, differentiation potential, neuronal maturation, synaptic density and functional activity. Deletion of the 1q21.1 locus was also associated with an increased expression of lower cortical layer markers. This difference was conserved in the mouse model of 1q21.1 deletion, which displayed altered corticogenesis. Importantly, we show that neurons with 1q21.1 deletion and duplication are associated with differential expression of calcium channels and demonstrate that physiological deficits in neurons with 1q21.1 deletion or duplication can be pharmacologically modulated by targeting Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channel activity. These findings provide biological insight into the neuropathological mechanism underlying 1q21.1 associated brain disorder and indicate a potential target for therapeutic interventions.\n                  <\/jats:p>","DOI":"10.1038\/s41380-021-01182-2","type":"journal-article","created":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T01:03:37Z","timestamp":1623287017000},"page":"819-830","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Using induced pluripotent stem cells to investigate human neuronal phenotypes in 1q21.1 deletion and duplication syndrome"],"prefix":"10.1038","volume":"27","author":[{"given":"Gareth","family":"Chapman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mouhamed","family":"Alsaqati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharna","family":"Lunn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie C.","family":"Linden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5638-9292","authenticated-orcid":false,"given":"David E. J.","family":"Linden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4426-3254","authenticated-orcid":false,"given":"Marianne B. M.","family":"van den Bree","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Ziller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4798-0862","authenticated-orcid":false,"given":"Michael J.","family":"Owen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0403-3278","authenticated-orcid":false,"given":"Jeremy","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian J.","family":"Harwood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9495-307X","authenticated-orcid":false,"given":"Yasir Ahmed","family":"Syed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,10]]},"reference":[{"key":"1182_CR1","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1038\/ng.909","volume":"43","author":"GM Cooper","year":"2011","unstructured":"Cooper GM, Coe BP, Girirajan S, Rosenfeld JA, Vu TH, Baker C, et al. A copy number variation morbidity map of developmental delay. Nat Genet. 2011;43:838\u201346.","journal-title":"Nat Genet"},{"key":"1182_CR2","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1038\/nature13394","volume":"511","author":"C Gilissen","year":"2014","unstructured":"Gilissen C, Hehir-Kwa JY, Thung DT, van de Vorst M, van Bon BW, Willemsen MH, et al. Genome sequencing identifies major causes of severe intellectual disability. Nature. 2014;511:344\u20137.","journal-title":"Nature"},{"key":"1182_CR3","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1038\/ng.3303","volume":"47","author":"N Krumm","year":"2015","unstructured":"Krumm N, Turner TN, Baker C, Vives L, Mohajeri K, Witherspoon K, et al. Excess of rare, inherited truncating mutations in autism. Nat Genet. 2015;47:582\u20138.","journal-title":"Nat Genet"},{"key":"1182_CR4","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/ng.3725","volume":"49","author":"CR Marshall","year":"2017","unstructured":"Marshall CR, Howrigan DP, Merico D, Thiruvahindrapuram B, Wu W, Greer DS, et al. Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects. Nat Genet. 2017;49:27\u201335.","journal-title":"Nat Genet"},{"key":"1182_CR5","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1016\/S0140-6736(10)61109-9","volume":"376","author":"NM Williams","year":"2010","unstructured":"Williams NM, Zaharieva I, Martin A, Langley K, Mantripragada K, Fossdal R, et al. Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis. Lancet. 2010;376:1401\u20138.","journal-title":"Lancet"},{"key":"1182_CR6","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/S2215-0366(19)30123-3","volume":"6","author":"S Chawner","year":"2019","unstructured":"Chawner S, Owen MJ, Holmans P, Raymond FL, Skuse D, Hall J, et al. Genotype-phenotype associations in children with copy number variants associated with high neuropsychiatric risk in the UK (IMAGINE-ID): a case-control cohort study. Lancet Psychiatry. 2019;6:493\u2013505.","journal-title":"Lancet Psychiatry"},{"key":"1182_CR7","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1111\/epi.14722","volume":"60","author":"CB Eaton","year":"2019","unstructured":"Eaton CB, Thomas RH, Hamandi K, Payne GC, Kerr MP, Linden DEJ, et al. Epilepsy and seizures in young people with 22q11.2 deletion syndrome: Prevalence and links with other neurodevelopmental disorders. Epilepsia. 2019;60:818\u201329.","journal-title":"Epilepsia"},{"key":"1182_CR8","doi-asserted-by":"publisher","first-page":"R45","DOI":"10.1093\/hmg\/ddv253","volume":"24","author":"G Kirov","year":"2015","unstructured":"Kirov G. CNVs in neuropsychiatric disorders. Hum Mol Genet. 2015;24:R45\u201349.","journal-title":"Hum Mol Genet"},{"key":"1182_CR9","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1136\/jmedgenet-2015-103366","volume":"53","author":"F Torres","year":"2016","unstructured":"Torres F, Barbosa M, Maciel P. Recurrent copy number variations as risk factors for neurodevelopmental disorders: critical overview and analysis of clinical implications. J Med Genet. 2016;53:73\u201390.","journal-title":"J Med Genet"},{"key":"1182_CR10","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-018-0339-8","volume":"9","author":"M Niarchou","year":"2019","unstructured":"Niarchou M, Chawner S, Doherty JL, Maillard AM, Jacquemont S, Chung WK, et al. Psychiatric disorders in children with 16p11.2 deletion and duplication. Transl Psychiatry. 2019;9:8.","journal-title":"Transl Psychiatry"},{"key":"1182_CR11","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1007\/s00439-014-1513-6","volume":"134","author":"M Woodbury-Smith","year":"2015","unstructured":"Woodbury-Smith M, Paterson AD, Thiruvahindrapduram B, Lionel AC, Marshall CR, Merico D, et al. Using extended pedigrees to identify novel autism spectrum disorder (ASD) candidate genes. Hum Genet. 2015;134:191\u2013201.","journal-title":"Hum Genet"},{"key":"1182_CR12","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/nature11011","volume":"485","author":"BM Neale","year":"2012","unstructured":"Neale BM, Kou Y, Liu L, Ma\u2019ayan A, Samocha KE, Sabo A, et al. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature. 2012;485:242\u20135.","journal-title":"Nature"},{"key":"1182_CR13","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1038\/ng.3638","volume":"48","author":"DM Ruderfer","year":"2016","unstructured":"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\u201311.","journal-title":"Nat Genet"},{"key":"1182_CR14","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1056\/NEJMoa0805384","volume":"359","author":"HC Mefford","year":"2008","unstructured":"Mefford HC, Sharp AJ, Baker C, Itsara A, Jiang Z, Buysse K, et al. Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. N. Engl J Med. 2008;359:1685\u201399.","journal-title":"N. Engl J Med"},{"key":"1182_CR15","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1038\/ng.279","volume":"40","author":"N Brunetti-Pierri","year":"2008","unstructured":"Brunetti-Pierri N, Berg JS, Scaglia F, Belmont J, Bacino CA, Sahoo T, et al. Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities. Nat Genet. 2008;40:1466\u201371.","journal-title":"Nat Genet"},{"key":"1182_CR16","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1086\/431652","volume":"77","author":"AJ Sharp","year":"2005","unstructured":"Sharp AJ, Locke DP, McGrath SD, Cheng Z, Bailey JA, Vallente RU, et al. Segmental duplications and copy-number variation in the human genome. Am J Hum Genet. 2005;77:78\u201388.","journal-title":"Am J Hum Genet"},{"key":"1182_CR17","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-018-5292-7","volume":"19","author":"D Owen","year":"2018","unstructured":"Owen D, Bracher-Smith M, Kendall KM, Rees E, Einon M, Escott-Price V, et al. Effects of pathogenic CNVs on physical traits in participants of the UK Biobank. BMC Genomics. 2018;19:867.","journal-title":"BMC Genomics"},{"key":"1182_CR18","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1038\/gim.2012.129","volume":"15","author":"A Dolcetti","year":"2013","unstructured":"Dolcetti A, Silversides CK, Marshall CR, Lionel AC, Stavropoulos DJ, Scherer SW, et al. 1q21.1 Microduplication expression in adults. Genet Med. 2013;15:282\u20139.","journal-title":"Genet Med"},{"key":"1182_CR19","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s13052-017-0380-x","volume":"43","author":"M Buse","year":"2017","unstructured":"Buse M, Cuttaia HC, Palazzo D, Mazara MV, Lauricella SA, Malacarne M, et al. Expanding the phenotype of reciprocal 1q21.1 deletions and duplications: a case series. Ital J Pediatr. 2017;43:61.","journal-title":"Ital J Pediatr"},{"key":"1182_CR20","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1038\/ejhg.2012.6","volume":"20","author":"JA Rosenfeld","year":"2012","unstructured":"Rosenfeld JA, Traylor RN, Schaefer GB, McPherson EW, Ballif BC, Klopocki E, et al. Proximal microdeletions and microduplications of 1q21.1 contribute to variable abnormal phenotypes. Eur J Hum Genet. 2012;20:754\u201361.","journal-title":"Eur J Hum Genet"},{"key":"1182_CR21","unstructured":"Cunningham AC, Hall J, Einfeld S, Owen MJ, consortium I-I, van den Bree MBM. Assessment of emotions and behaviour by the Developmental Behaviour Checklist in young people with neurodevelopmental CNVs. Psychol Med. 2020:1\u201313. https:\/\/www.cambridge.org\/core\/journals\/psychological-medicine\/article\/assessment-of-emotions-and-behaviour-by-the-developmental-behaviourchecklist-in-young-people-with-neurodevelopmental-cnvs\/D26B0837601A9C195D3534A86670EA02."},{"key":"1182_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-50226-9","volume":"9","author":"W Plumbly","year":"2019","unstructured":"Plumbly W, Brandon N, Deeb TZ, Hall J, Harwood AJ. L-type voltage-gated calcium channel regulation of in vitro human cortical neuronal networks. Sci Rep. 2019;9:13810.","journal-title":"Sci Rep"},{"key":"1182_CR23","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1038\/nbt.2249","volume":"30","author":"SM Chambers","year":"2012","unstructured":"Chambers SM, Qi Y, Mica Y, Lee G, Zhang XJ, Niu L, et al. Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors. Nat Biotechnol. 2012;30:715\u201320.","journal-title":"Nat Biotechnol"},{"key":"1182_CR24","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/0092-8674(90)90662-X","volume":"60","author":"U Lendahl","year":"1990","unstructured":"Lendahl U, Zimmerman LB, McKay RD. CNS stem cells express a new class of intermediate filament protein. Cell. 1990;60:585\u201395.","journal-title":"Cell"},{"key":"1182_CR25","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/S0896-6273(00)80778-3","volume":"23","author":"JG Gleeson","year":"1999","unstructured":"Gleeson JG, Lin PT, Flanagan LA, Walsh CA. Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons. Neuron. 1999;23:257\u201371.","journal-title":"Neuron"},{"key":"1182_CR26","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1083\/jcb.200110134","volume":"158","author":"A Harada","year":"2002","unstructured":"Harada A, Teng J, Takei Y, Oguchi K, Hirokawa N. MAP2 is required for dendrite elongation, PKA anchoring in dendrites, and proper PKA signal transduction. J Cell Biol. 2002;158:541\u20139.","journal-title":"J Cell Biol"},{"key":"1182_CR27","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1038\/nm.2576","volume":"17","author":"SP Pasca","year":"2011","unstructured":"Pasca SP, Portmann T, Voineagu I, Yazawa M, Shcheglovitov A, Pasca AM, et al. Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome. Nat Med. 2011;17:1657\u201362.","journal-title":"Nat Med"},{"key":"1182_CR28","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1016\/j.celrep.2019.01.023","volume":"26","author":"K Meyer","year":"2019","unstructured":"Meyer K, Feldman HM, Lu T, Drake D, Lim ET, Ling KH, et al. REST and neural gene network dysregulation in iPSC models of Alzheimer\u2019s disease. Cell Rep. 2019;26:1112\u201327. e1119","journal-title":"Cell Rep"},{"key":"1182_CR29","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1111\/j.1469-7610.2010.02307.x","volume":"52","author":"JL Rubenstein","year":"2011","unstructured":"Rubenstein JL. Annual research review: development of the cerebral cortex: implications for neurodevelopmental disorders. J Child Psychol Psychiatry. 2011;52:339\u201355.","journal-title":"J Child Psychol Psychiatry"},{"key":"1182_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-017-0011-8","volume":"7","author":"J Nielsen","year":"2017","unstructured":"Nielsen J, Fejgin K, Sotty F, Nielsen V, Mork A, Christoffersen CT, et al. A mouse model of the schizophrenia-associated 1q21.1 microdeletion syndrome exhibits altered mesolimbic dopamine transmission. Transl Psychiatry. 2017;7:1261.","journal-title":"Transl Psychiatry"},{"key":"1182_CR31","doi-asserted-by":"publisher","first-page":"1893","DOI":"10.1002\/glia.23666","volume":"67","author":"SD Klapper","year":"2019","unstructured":"Klapper SD, Garg P, Dagar S, Lenk K, Gottmann K, Nieweg K. Astrocyte lineage cells are essential for functional neuronal differentiation and synapse maturation in human iPSC-derived neural networks. Glia. 2019;67:1893\u2013909.","journal-title":"Glia"},{"key":"1182_CR32","doi-asserted-by":"publisher","DOI":"10.1038\/srep26181","volume":"6","author":"A Odawara","year":"2016","unstructured":"Odawara A, Katoh H, Matsuda N, Suzuki I. Physiological maturation and drug responses of human induced pluripotent stem cell-derived cortical neuronal networks in long-term culture. Sci Rep. 2016;6:26181.","journal-title":"Sci Rep"},{"key":"1182_CR33","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/sj.bjp.0702574","volume":"127","author":"D Dobrev","year":"1999","unstructured":"Dobrev D, Milde AS, Andreas K, Ravens U. The effects of verapamil and diltiazem on N-, P- and Q-type calcium channels mediating dopamine release in rat striatum. Br J Pharm. 1999;127:576\u201382.","journal-title":"Br J Pharm"},{"key":"1182_CR34","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1139\/y83-209","volume":"61","author":"JF MacDonald","year":"1983","unstructured":"MacDonald JF, Schneiderman JH. Actions of verapamil on the excitability of cultured neurones. Can J Physiol Pharm. 1983;61:1467\u201372.","journal-title":"Can J Physiol Pharm"},{"key":"1182_CR35","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.1529\/biophysj.104.052837","volume":"89","author":"Z Buraei","year":"2005","unstructured":"Buraei Z, Anghelescu M, Elmslie KS. Slowed N-type calcium channel (CaV2.2) deactivation by the cyclin-dependent kinase inhibitor roscovitine. Biophys J. 2005;89:1681\u201391.","journal-title":"Biophys J"},{"key":"1182_CR36","doi-asserted-by":"publisher","first-page":"10559","DOI":"10.1523\/JNEUROSCI.4629-12.2013","volume":"33","author":"TB Tarr","year":"2013","unstructured":"Tarr TB, Malick W, Liang M, Valdomir G, Frasso M, Lacomis D, et al. Evaluation of a novel calcium channel agonist for therapeutic potential in Lambert-Eaton myasthenic syndrome. J Neurosci. 2013;33:10559\u201367.","journal-title":"J Neurosci"},{"key":"1182_CR37","doi-asserted-by":"publisher","first-page":"2066","DOI":"10.1101\/gr.180893.114","volume":"24","author":"KM Steinberg","year":"2014","unstructured":"Steinberg KM, Schneider VA, Graves-Lindsay TA, Fulton RS, Agarwala R, Huddleston J, et al. Single haplotype assembly of the human genome from a hydatidiform mole. Genome Res. 2014;24:2066\u201376.","journal-title":"Genome Res"},{"key":"1182_CR38","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1016\/j.cell.2018.03.051","volume":"173","author":"IT Fiddes","year":"2018","unstructured":"Fiddes IT, Lodewijk GA, Mooring M, Bosworth CM, Ewing AD, Mantalas GL, et al. Human-specific NOTCH2NL genes affect notch signaling and cortical neurogenesis. Cell. 2018;173:1356\u201369. e1322","journal-title":"Cell"},{"key":"1182_CR39","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.ajhg.2018.01.006","volume":"102","author":"M Uddin","year":"2018","unstructured":"Uddin M, Unda BK, Kwan V, Holzapfel NT, White SH, Chalil L, et al. OTUD7A regulates neurodevelopmental phenotypes in the 15q13.3 microdeletion syndrome. Am J Hum Genet. 2018;102:278\u201395.","journal-title":"Am J Hum Genet"},{"key":"1182_CR40","doi-asserted-by":"publisher","first-page":"2678","DOI":"10.1016\/j.celrep.2017.11.037","volume":"21","author":"A Deshpande","year":"2017","unstructured":"Deshpande A, Yadav S, Dao DQ, Wu ZY, Hokanson KC, Cahill MK, et al. Cellular phenotypes in human iPSC-derived neurons from a genetic model of autism spectrum disorder. Cell Rep. 2017;21:2678\u201387.","journal-title":"Cell Rep"},{"key":"1182_CR41","first-page":"3561","volume":"39","author":"A Gokhale","year":"2019","unstructured":"Gokhale A, Hartwig C, Freeman AAH, Bassell JL, Zlatic SA, Sapp Savas C, et al. Systems analysis of the 22q11.2 microdeletion syndrome converges on a mitochondrial interactome necessary for synapse function and behavior. J Neurosci. 2019;39:3561\u201381.","journal-title":"J Neurosci"},{"key":"1182_CR42","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1124\/mol.51.5.872","volume":"51","author":"D Cai","year":"1997","unstructured":"Cai D, Mulle JG, Yue DT. Inhibition of recombinant Ca2+ channels by benzothiazepines and phenylalkylamines: class-specific pharmacology and underlying molecular determinants. Mol Pharm. 1997;51:872\u201381.","journal-title":"Mol Pharm"},{"key":"1182_CR43","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.ejphar.2007.06.050","volume":"573","author":"B Tarabova","year":"2007","unstructured":"Tarabova B, Lacinova L, Engel J. Effects of phenylalkylamines and benzothiazepines on Ca(v)1.3-mediated Ca2+ currents in neonatal mouse inner hair cells. Eur J Pharm. 2007;573:39\u201348.","journal-title":"Eur J Pharm"},{"key":"1182_CR44","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1038\/mp.2016.86","volume":"21","author":"A Cipriani","year":"2016","unstructured":"Cipriani A, Saunders K, Attenburrow MJ, Stefaniak J, Panchal P, Stockton S, et al. A systematic review of calcium channel antagonists in bipolar disorder and some considerations for their future development. Mol Psychiatry. 2016;21:1324\u201332.","journal-title":"Mol Psychiatry"},{"key":"1182_CR45","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1007\/s00210-013-0866-z","volume":"386","author":"G Biala","year":"2013","unstructured":"Biala G, Kruk-Slomka M, Jozwiak K. Influence of acute or chronic calcium channel antagonists on the acquisition and consolidation of memory and nicotine-induced cognitive effects in mice. Naunyn Schmiedebergs Arch Pharm. 2013;386:651\u201364.","journal-title":"Naunyn Schmiedebergs Arch Pharm"},{"key":"1182_CR46","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.nlm.2003.10.003","volume":"81","author":"BL Woodside","year":"2004","unstructured":"Woodside BL, Borroni AM, Hammonds MD, Teyler TJ. NMDA receptors and voltage-dependent calcium channels mediate different aspects of acquisition and retention of a spatial memory task. Neurobiol Learn Mem. 2004;81:105\u201314.","journal-title":"Neurobiol Learn Mem"},{"key":"1182_CR47","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1074\/jbc.M109.076448","volume":"285","author":"V Yarotskyy","year":"2010","unstructured":"Yarotskyy V, Gao G, Du L, Ganapathi SB, Peterson BZ, Elmslie KS. Roscovitine binds to novel L-channel (CaV1.2) sites that separately affect activation and inactivation. J Biol Chem. 2010;285:43\u201353.","journal-title":"J Biol Chem"},{"key":"1182_CR48","doi-asserted-by":"publisher","first-page":"2590","DOI":"10.1523\/JNEUROSCI.22-07-02590.2002","volume":"22","author":"K Tomizawa","year":"2002","unstructured":"Tomizawa K, Ohta J, Matsushita M, Moriwaki A, Li ST, Takei K, et al. Cdk5\/p35 regulates neurotransmitter release through phosphorylation and downregulation of P\/Q-type voltage-dependent calcium channel activity. J Neurosci. 2002;22:2590\u20137.","journal-title":"J Neurosci"}],"container-title":["Molecular Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41380-021-01182-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-021-01182-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-021-01182-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T08:04:45Z","timestamp":1651219485000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41380-021-01182-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,10]]},"references-count":48,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["1182"],"URL":"https:\/\/doi.org\/10.1038\/s41380-021-01182-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.02.08.430246","asserted-by":"object"}]},"ISSN":["1359-4184","1476-5578"],"issn-type":[{"value":"1359-4184","type":"print"},{"value":"1476-5578","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,10]]},"assertion":[{"value":"16 February 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 May 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 May 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 June 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Generation and use of human iPSC were approved by the Cardiff University and HSE (GMO130\/19.3). Clinical and psychometric testing (supplementary table 1) of participants and skin biopsies was approved by the Regional Ethics Committee of the National Health Service (study 14\/WA\/0035).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics statement"}}]}}