{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:30:53Z","timestamp":1791415853762,"version":"4.3.3"},"reference-count":70,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T00:00:00Z","timestamp":1549929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T00:00:00Z","timestamp":1549929600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T00:00:00Z","timestamp":1549929600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007631","name":"Canadian Institute for Advanced Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007631","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000196","name":"Canada Foundation for Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008914","name":"Ontario Brain Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008914","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Province of Ontario Neurodevelopmental Disorders"},{"name":"Ontario Research Fund"},{"DOI":"10.13039\/100008762","name":"Genome Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008762","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Toronto McLaughlin Centre"},{"DOI":"10.13039\/100000073","name":"Autism Speaks","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000073","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006126","name":"Hospital for Sick Children","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006126","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Induced pluripotent stem cell (iPSC)-derived neurons are increasingly used to model Autism Spectrum Disorder (ASD), which is clinically and genetically heterogeneous. To study the complex relationship of penetrant and weaker polygenic risk variants to ASD, \u2018isogenic\u2019 iPSC-derived neurons are critical. We developed a set of procedures to control for heterogeneity in reprogramming and differentiation, and generated 53 different iPSC-derived glutamatergic neuronal lines from 25 participants from 12 unrelated families with ASD. Heterozygous de novo and rare-inherited presumed-damaging variants were characterized in ASD risk genes\/loci. Combinations of putative etiologic variants (GLI3\/KIF21A or EHMT2\/UBE2I) in separate families were modeled. We used a multi-electrode array, with patch-clamp recordings, to determine a reproducible synaptic phenotype in 25% of the individuals with ASD (other relevant data on the remaining lines was collected). Our most compelling new results revealed a consistent spontaneous network hyperactivity in neurons deficient for CNTN5 or EHMT2. The biobank of iPSC-derived neurons and accompanying genomic data are available to accelerate ASD research.<\/jats:p>\n                  <jats:p>Editorial note: This article has been through an editorial process in which authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (&lt;xref ref-type=\"decision-letter\" rid=\"SA1\"&gt;see decision letter&lt;\/xref&gt;).<\/jats:p>","DOI":"10.7554\/elife.40092","type":"journal-article","created":{"date-parts":[[2019,2,11]],"date-time":"2019-02-11T19:00:39Z","timestamp":1549911639000},"source":"Crossref","is-referenced-by-count":105,"title":["CNTN5-\/+or EHMT2-\/+human iPSC-derived neurons from individuals with autism develop hyperactive neuronal networks"],"prefix":"10.7554","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6875-0380","authenticated-orcid":true,"given":"Eric","family":"Deneault","sequence":"first","affiliation":[{"name":"Genetics & Genome Biology Program, The Hospital for Sick Children, Toronto, Canada"},{"name":"The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, 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L","family":"Howe","sequence":"additional","affiliation":[{"name":"Genetics & Genome Biology Program, The Hospital for Sick Children, Toronto, Canada"},{"name":"The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Chalil","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vickie","family":"Kwan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Walker","sequence":"additional","affiliation":[{"name":"Genetics & Genome Biology Program, The Hospital for Sick Children, Toronto, 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