{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:45:46Z","timestamp":1789865146677,"version":"4.0.1"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T00:00:00Z","timestamp":1636588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54NS093793"],"award-info":[{"award-number":["U54NS093793"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DC014932"],"award-info":[{"award-number":["R01DC014932"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R24OD022005"],"award-info":[{"award-number":["R24OD022005"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>FZR1, which encodes the Cdh1 subunit of the anaphase-promoting complex, plays an important role in neurodevelopment by regulating the cell cycle and by its multiple post-mitotic functions in neurons. In this study, evaluation of 250 unrelated patients with developmental and epileptic encephalopathies and a connection on GeneMatcher led to the identification of three de novo missense variants in FZR1.<\/jats:p>\n                  <jats:p>Whole-exome sequencing in 39 patient\u2013parent trios and subsequent targeted sequencing in an additional cohort of 211 patients was performed to identify novel genes involved in developmental and epileptic encephalopathy. Functional studies in Drosophila were performed using three different mutant alleles of the Drosophila homologue of FZR1 fzr.<\/jats:p>\n                  <jats:p>All three individuals carrying de novo variants in FZR1 had childhood-onset generalized epilepsy, intellectual disability, mild ataxia and normal head circumference. Two individuals were diagnosed with the developmental and epileptic encephalopathy subtype myoclonic atonic epilepsy. We provide genetic-association testing using two independent statistical tests to support FZR1 association with developmental and epileptic encephalopathies. Further, we provide functional evidence that the missense variants are loss-of-function alleles using Drosophila neurodevelopment assays. Using three fly mutant alleles of the Drosophila homologue fzr and overexpression studies, we show that patient variants can affect proper neurodevelopment.<\/jats:p>\n                  <jats:p>With the recent report of a patient with neonatal-onset with microcephaly who also carries a de novo FZR1 missense variant, our study consolidates the relationship between FZR1 and developmental and epileptic encephalopathy and expands the associated phenotype. We conclude that heterozygous loss-of-function of FZR1 leads to developmental and epileptic encephalopathies associated with a spectrum of neonatal to childhood-onset seizure types, developmental delay and mild ataxia. Microcephaly can be present but is not an essential feature of FZR1-encephalopathy. In summary, our approach of targeted sequencing using novel gene candidates and functional testing in Drosophila will help solve undiagnosed myoclonic atonic epilepsy or developmental and epileptic encephalopathy cases.<\/jats:p>","DOI":"10.1093\/brain\/awab409","type":"journal-article","created":{"date-parts":[[2021,11,6]],"date-time":"2021-11-06T08:12:52Z","timestamp":1636186372000},"page":"1684-1697","source":"Crossref","is-referenced-by-count":18,"title":["<i>De novo FZR1<\/i>\n                    loss-of-function variants cause developmental and epileptic encephalopathies"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9470-2390","authenticated-orcid":false,"given":"Sathiya N","family":"Manivannan","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine , Houston, TX 77030, USA"},{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital , Houston 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolien","family":"Roovers","sequence":"additional","affiliation":[{"name":"Neurogenetics Group, VIB Centre for Molecular Neurology , Antwerp 2610, Belgium"},{"name":"Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp , Antwerp 2610, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noor","family":"Smal","sequence":"additional","affiliation":[{"name":"Applied and Translational Neurogenomics Group, VIB Centre for Molecular Neurology, VIB , Antwerp 2610, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candace T","family":"Myers","sequence":"additional","affiliation":[{"name":"Center for Pediatric Neurological Disease Research, Department of Cell and Molecular Biology St. Jude Children\u2019s Research Hospital , Memphis, TN 30105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilsad","family":"Turkdogan","sequence":"additional","affiliation":[{"name":"Division of Child Neurology, Department of Paediatrics, Marmara University, Faculty of Medicine , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"Roelens","sequence":"additional","affiliation":[{"name":"Child Neurology, AZ Delta , Roeselare, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oguz","family":"Kanca","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine , Houston, TX 77030, USA"},{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital , Houston 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung-Lok","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine , Houston, TX 77030, USA"},{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital , Houston 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tasja","family":"Scholz","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Medical Centre Hamburg-Eppendorf , 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Hermann","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University Medical Centre Hamburg-Eppendorf , 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Bierhals","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Medical Centre Hamburg-Eppendorf , 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hande S","family":"Caglayan","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Bogazici University , Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Stamberger","sequence":"additional","affiliation":[{"name":"Applied and Translational Neurogenomics Group, VIB Centre for Molecular Neurology, VIB , Antwerp 2610, Belgium"},{"name":"Department of Neurology, University Hospital Antwerp , Antwerp 2650, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"MAE Working Group of EuroEPINOMICS RES Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Craiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Davila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Helbig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzo","family":"Guerrini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Elina","family":"Lehesjoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Marini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiltrud","family":"Muhle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikke S","family":"M\u00f8ller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Neubauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deb","family":"Pal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin","family":"Sterbova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Striano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiina","family":"Talvik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"von Spiczak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Hoffman-Zacharska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Mefford","sequence":"additional","affiliation":[{"name":"Center for Pediatric Neurological Disease Research, Department of Cell and Molecular Biology St. Jude Children\u2019s Research Hospital , Memphis, TN 30105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"de Jonghe","sequence":"additional","affiliation":[{"name":"Neurogenetics Group, VIB Centre for Molecular Neurology , Antwerp 2610, Belgium"},{"name":"Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp , Antwerp 2610, Belgium"},{"name":"Department of Neurology, University Hospital Antwerp , Antwerp 2650, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2172-8036","authenticated-orcid":false,"given":"Shinya","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine , Houston, TX 77030, USA"},{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital , Houston 77030, USA"},{"name":"Department of Neuroscience, Baylor College of Medicine , Houston, TX 77030, USA"},{"name":"Program in Developmental Biology, Baylor College of Medicine , Houston, TX 77030, USA"},{"name":"Development, Disease Models & Therapeutics Graduate Program, Baylor College of Medicine , Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2878-1147","authenticated-orcid":false,"given":"Sarah","family":"Weckhuysen","sequence":"additional","affiliation":[{"name":"Applied and Translational Neurogenomics Group, VIB Centre for Molecular Neurology, VIB , Antwerp 2610, Belgium"},{"name":"Department of Neurology, University Hospital Antwerp , Antwerp 2650, Belgium"},{"name":"Translational Neurosciences, Faculty of Medicine and Health Science, University of Antwerp , Antwerp 2650, Belgium"},{"name":"\u00b5NEURO Research Centre of Excellence, University of Antwerp , Antwerp 2610, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo J","family":"Bellen","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine , Houston, TX 77030, USA"},{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital , Houston 77030, USA"},{"name":"Department of Neuroscience, Baylor College of Medicine , Houston, TX 77030, USA"},{"name":"Program in Developmental Biology, Baylor College of Medicine , Houston, TX 77030, USA"},{"name":"Development, Disease Models & Therapeutics Graduate Program, Baylor College of Medicine , Houston, TX 77030, USA"},{"name":"Howard Hughes Medical Institute, Baylor College of Medicine , Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,11,11]]},"reference":[{"issue":"4","key":"2022060319043402100_awab409-B1","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1111\/epi.13709","article-title":"ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology","volume":"58","author":"Scheffer","year":"2017","journal-title":"Epilepsia"},{"issue":"3","key":"2022060319043402100_awab409-B2","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/epi4.12348","article-title":"Possible precision medicine implications from genetic testing using combined detection of sequence and intragenic copy number variants in a large cohort with childhood epilepsy","volume":"4","author":"Truty","year":"2019","journal-title":"Epilepsia Open"},{"issue":"3","key":"2022060319043402100_awab409-B3","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/S1474-4422(15)00250-1","article-title":"The genetic landscape of the epileptic encephalopathies of infancy and childhood","volume":"15","author":"McTague","year":"2016","journal-title":"Lancet Neurol"},{"issue":"5","key":"2022060319043402100_awab409-B4","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/nrneurol.2014.62","article-title":"The hidden genetics of epilepsy\u2014A clinically important new paradigm","volume":"10","author":"Thomas","year":"2014","journal-title":"Nat Rev Neurol"},{"issue":"1","key":"2022060319043402100_awab409-B5","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/epi.14618","article-title":"Diagnostic exome sequencing in 100 consecutive patients with both epilepsy and intellectual disability","volume":"60","author":"Snoeijen-Schouwenaars","year":"2019","journal-title":"Epilepsia"},{"key":"2022060319043402100_awab409-B6","doi-asserted-by":"crossref","first-page":"434","DOI":"10.3389\/fneur.2019.00434","article-title":"Diagnostic yield and treatment impact of targeted exome sequencing in early-onset epilepsy","volume":"10","author":"Demos","year":"2019","journal-title":"Front Neurol"},{"issue":"12","key":"2022060319043402100_awab409-B7","doi-asserted-by":"crossref","first-page":"e203-8","DOI":"10.1111\/epi.13222","article-title":"The role of SLC2A1 mutations in myoclonic astatic epilepsy and absence epilepsy, and the estimated frequency of GLUT1 deficiency syndrome","volume":"56","author":"Larsen","year":"2015","journal-title":"Epilepsia"},{"issue":"5","key":"2022060319043402100_awab409-B8","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1111\/epi.16508","article-title":"Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures","volume":"61","author":"Tang","year":"2020","journal-title":"Epilepsia"},{"issue":"10","key":"2022060319043402100_awab409-B9","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1002\/humu.22844","article-title":"GeneMatcher: A matching tool for connecting investigators with an interest in the same gene","volume":"36","author":"Sobreira","year":"2015","journal-title":"Human Mutation"},{"issue":"7518","key":"2022060319043402100_awab409-B10","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1038\/nature13543","article-title":"Molecular architecture and mechanism of the anaphase-promoting complex","volume":"513","author":"Chang","year":"2014","journal-title":"Nature"},{"issue":"2","key":"2022060319043402100_awab409-B11","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S1097-2765(00)80126-4","article-title":"Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1","volume":"2","author":"Fang","year":"1998","journal-title":"Mol Cell"},{"issue":"22","key":"2022060319043402100_awab409-B12","doi-asserted-by":"crossref","first-page":"6499","DOI":"10.1093\/emboj\/20.22.6499","article-title":"Activation of Cdh1-dependent APC is required for G1 cell cycle arrest and DNA damage-induced G2 checkpoint in vertebrate cells","volume":"20","author":"Sudo","year":"2001","journal-title":"EMBO J"},{"issue":"7","key":"2022060319043402100_awab409-B13","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1038\/ncb1742","article-title":"Genomic stability and tumour suppression by the APC\/C cofactor Cdh1","volume":"10","author":"Garc\u00eda-Higuera","year":"2008","journal-title":"Nat Cell Biol"},{"key":"2022060319043402100_awab409-B14","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1038\/ncomms3879","article-title":"APC\/C-Cdh1 coordinates neurogenesis and cortical size during development","volume":"4","author":"Delgado-Esteban","year":"2013","journal-title":"Nat Commun"},{"issue":"6","key":"2022060319043402100_awab409-B15","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1101\/gad.274324.115","article-title":"A decade of the anaphase-promoting complex in the nervous system","volume":"30","author":"Huang","year":"2016","journal-title":"Genes Dev"},{"key":"2022060319043402100_awab409-B16","doi-asserted-by":"crossref","first-page":"104613","DOI":"10.1016\/j.neuint.2019.104613","article-title":"Upregulation of Cdh1 in the trigeminal spinal subnucleus caudalis attenuates trigeminal neuropathic pain via inhibiting GABAergic neuronal apoptosis","volume":"133","author":"Li","year":"2020","journal-title":"Neurochem Int"},{"issue":"1","key":"2022060319043402100_awab409-B17","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s10571-018-0638-x","article-title":"APC-Cdh1 regulates neuronal apoptosis through modulating glycolysis and pentose-phosphate pathway after oxygen-glucose deprivation and reperfusion","volume":"39","author":"Li","year":"2019","journal-title":"Cell Mol Neurobiol"},{"issue":"24","key":"2022060319043402100_awab409-B18","doi-asserted-by":"crossref","first-page":"4673","DOI":"10.1242\/dev.152694","article-title":"Different modes of APC\/C activation control growth and neuron\u2013glia interaction in the developing Drosophila eye","volume":"144","author":"Neuert","year":"2017","journal-title":"Development"},{"issue":"17","key":"2022060319043402100_awab409-B19","doi-asserted-by":"crossref","first-page":"4513","DOI":"10.1073\/pnas.1616024114","article-title":"APC\/C(Cdh1)-Rock2 pathway controls dendritic integrity and memory","volume":"114","author":"Bobo-Jimenez","year":"2017","journal-title":"Proc Natl Acad Sci USA"},{"issue":"11","key":"2022060319043402100_awab409-B20","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1038\/nn.2656","article-title":"APC\/C(Fzr\/Cdh1)-dependent regulation of cell adhesion controls glial migration in the Drosophila PNS","volume":"13","author":"Silies","year":"2010","journal-title":"Nat Neurosci"},{"issue":"4","key":"2022060319043402100_awab409-B21","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/S0092-8674(00)80528-0","article-title":"Drosophila fizzy-related down-regulates mitotic cyclins and is required for cell proliferation arrest and entry into endocycles","volume":"90","author":"Sigrist","year":"1997","journal-title":"Cell"},{"issue":"2","key":"2022060319043402100_awab409-B22","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.ydbio.2005.07.011","article-title":"rap gene encodes Fizzy-related protein (Fzr) and regulates cell proliferation and pattern formation in the developing Drosophila eye-antennal disc","volume":"285","author":"Pimentel","year":"2005","journal-title":"Dev Biol"},{"issue":"1","key":"2022060319043402100_awab409-B23","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.cell.2014.09.002","article-title":"A drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases","volume":"159","author":"Yamamoto","year":"2014","journal-title":"Cell"},{"issue":"12A","key":"2022060319043402100_awab409-B24","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1101\/gad.3.12a.1834","article-title":"Neuronal development in the Drosophila compound eye: Rap gene function is required in photoreceptor cell R8 for ommatidial pattern formation","volume":"3","author":"Karpilow","year":"1989","journal-title":"Genes Dev"},{"issue":"1","key":"2022060319043402100_awab409-B25","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/jnc.14828","article-title":"A novel human Cdh1 mutation impairs anaphase promoting complex\/cyclosome activity resulting in microcephaly, psychomotor retardation, and epilepsy","volume":"151","author":"Rodriguez","year":"2019","journal-title":"J Neurochem"},{"key":"2022060319043402100_awab409-B26","doi-asserted-by":"crossref","first-page":"e35574","DOI":"10.7554\/eLife.35574","article-title":"A gene-specific T2A-GAL4 library for drosophila","volume":"7","author":"Lee","year":"2018","journal-title":"Elife"},{"issue":"5","key":"2022060319043402100_awab409-B27","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/j.ajhg.2013.09.017","article-title":"De novo loss-of-function mutations in CHD2 cause a fever-sensitive myoclonic epileptic encephalopathy sharing features with Dravet syndrome","volume":"93","author":"Suls","year":"2013","journal-title":"Am J Hum Genet"},{"issue":"7616","key":"2022060319043402100_awab409-B28","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nature19057","article-title":"Analysis of protein-coding genetic variation in 60,706 humans","volume":"536","author":"Lek","year":"2016","journal-title":"Nature"},{"issue":"7809","key":"2022060319043402100_awab409-B29","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"issue":"6235","key":"2022060319043402100_awab409-B30","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1126\/science.1262110","article-title":"The Genotype\u2013Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans","volume":"348","author":"Human Genomics","year":"2015","journal-title":"Science (New York, NY)"},{"issue":"D1","key":"2022060319043402100_awab409-B31","doi-asserted-by":"crossref","first-page":"D886","DOI":"10.1093\/nar\/gky1016","article-title":"CADD: Predicting the deleteriousness of variants throughout the human genome","volume":"47","author":"Rentzsch","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"2022060319043402100_awab409-B32","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.ajhg.2015.02.016","article-title":"Mutations in the GABA transporter SLC6A1 cause epilepsy with myoclonic\u2013atonic seizures","volume":"96","author":"Carvill","year":"2015","journal-title":"Am J Hum Genet"},{"issue":"7","key":"2022060319043402100_awab409-B33","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/nprot.2009.86","article-title":"Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm","volume":"4","author":"Kumar","year":"2009","journal-title":"Nat Protocols"},{"issue":"4","key":"2022060319043402100_awab409-B34","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat Methods"},{"issue":"10","key":"2022060319043402100_awab409-B35","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1101\/gr.174615.114","article-title":"Large-scale identification of chemically induced mutations in Drosophila melanogaster","volume":"24","author":"Haelterman","year":"2014","journal-title":"Genome Res"},{"key":"2022060319043402100_awab409-B36","doi-asserted-by":"crossref","first-page":"e26420","DOI":"10.7554\/eLife.26420","article-title":"A cell cycle-independent, conditional gene inactivation strategy for differentially tagging wild-type and mutant cells","volume":"6","author":"Nagarkar-Jaiswal","year":"2017","journal-title":"Elife"},{"key":"2022060319043402100_awab409-B37","first-page":"7.25.1","article-title":"Interpreting de novo variation in human disease using denovolyzeR","volume":"87","author":"Ware","year":"2015","journal-title":"Curr Protoc Hum Genet"},{"issue":"1","key":"2022060319043402100_awab409-B38","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13059-016-0974-4","article-title":"The ensembl variant effect predictor","volume":"17","author":"McLaren","year":"2016","journal-title":"Genome Biol"},{"issue":"7","key":"2022060319043402100_awab409-B39","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat Methods"},{"issue":"1","key":"2022060319043402100_awab409-B40","doi-asserted-by":"crossref","first-page":"26","DOI":"10.14348\/molcells.2020.0169","article-title":"Molecular analysis of the interaction between human PTPN21 and the oncoprotein E7 from human papillomavirus genotype 18","volume":"44","author":"Lee","year":"2021","journal-title":"Mol Cells"},{"issue":"4","key":"2022060319043402100_awab409-B41","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/j.cub.2020.11.014","article-title":"PTPN21\/Pez is a novel and evolutionarily conserved key regulator of inflammation in vivo","volume":"31","author":"Campbell","year":"2021","journal-title":"Curr Biol"},{"issue":"1-3","key":"2022060319043402100_awab409-B42","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.schres.2011.06.023","article-title":"Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia","volume":"131","author":"Chen","year":"2011","journal-title":"Schizophrenia Res"},{"issue":"1","key":"2022060319043402100_awab409-B43","doi-asserted-by":"crossref","first-page":"2693","DOI":"10.1038\/s41467-019-10644-9","article-title":"PTPN21 and Hook3 relieve KIF1C autoinhibition and activate intracellular transport","volume":"10","author":"Siddiqui","year":"2019","journal-title":"Nat Commun"},{"key":"2022060319043402100_awab409-B44","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.biocel.2015.02.003","article-title":"PTPN21 exerts pro-neuronal survival and neuritic elongation via ErbB4\/NRG3 signaling","volume":"61","author":"Plani-Lam","year":"2015","journal-title":"Int J Biochem Cell Biol"},{"issue":"1","key":"2022060319043402100_awab409-B45","doi-asserted-by":"crossref","first-page":"e201812044","DOI":"10.1083\/jcb.201812044","article-title":"Tumor protein D54 defines a new class of intracellular transport vesicles","volume":"219","author":"Larocque","year":"2020","journal-title":"J Cell Biol"},{"issue":"3","key":"2022060319043402100_awab409-B46","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s13402-013-0131-y","article-title":"Tumor protein D54 is a negative regulator of extracellular matrix-dependent migration and attachment in oral squamous cell carcinoma-derived cell lines","volume":"36","author":"Mukudai","year":"2013","journal-title":"Cell Oncol (Dordrecht)"},{"issue":"10","key":"2022060319043402100_awab409-B47","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.tibs.2010.04.003","article-title":"WD40 proteins propel cellular networks","volume":"35","author":"Stirnimann","year":"2010","journal-title":"Trends Biochem Sci"},{"issue":"2","key":"2022060319043402100_awab409-B48","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.ajhg.2019.06.014","article-title":"De novo variants in WDR37 are associated with epilepsy, colobomas, dysmorphism, developmental delay, intellectual disability, and cerebellar hypoplasia","volume":"105","author":"Kanca","year":"2019","journal-title":"Am J Hum Genet"},{"issue":"4","key":"2022060319043402100_awab409-B49","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1242\/dev.127.4.851","article-title":"Analysis of Drosophila photoreceptor axon guidance in eye-specific mosaics","volume":"127","author":"Newsome","year":"2000","journal-title":"Development"},{"issue":"5","key":"2022060319043402100_awab409-B50","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S0166-2236(00)01791-4","article-title":"Mosaic analysis with a repressible cell marker (MARCM) for Drosophila neural development","volume":"24","author":"Lee","year":"2001","journal-title":"Trends Neurosci"},{"issue":"6","key":"2022060319043402100_awab409-B51","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1002\/neu.480240604","article-title":"Gene elav of Drosophila melanogaster: A prototype for neuronal-specific RNA binding protein gene family that is conserved in flies and humans","volume":"24","author":"Yao","year":"1993","journal-title":"J Neurobiol"},{"issue":"3","key":"2022060319043402100_awab409-B52","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S0896-6273(00)80701-1","article-title":"Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis","volume":"22","author":"Lee","year":"1999","journal-title":"Neuron"},{"issue":"1","key":"2022060319043402100_awab409-B53","doi-asserted-by":"crossref","first-page":"37","DOI":"10.4045\/tidsskr.12.1344","article-title":"The role of glial cells in epilepsy","volume":"134","author":"Heuser","year":"2014","journal-title":"Tidsskr Nor Laegeforening"},{"issue":"6","key":"2022060319043402100_awab409-B54","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1177\/1535759720948890","article-title":"Epilepsy with myoclonic atonic seizures: Why is the yield of genetic testing for a \u2018presumed genetic\u2019 epilepsy low?","volume":"20","author":"Nickels","year":"2020","journal-title":"Epilepsy Curr"},{"issue":"2","key":"2022060319043402100_awab409-B55","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.celrep.2015.03.016","article-title":"Casein kinase 1\u03b4 is an APC\/C(Cdh1) substrate that regulates cerebellar granule cell neurogenesis","volume":"11","author":"Penas","year":"2015","journal-title":"Cell Rep"},{"key":"2022060319043402100_awab409-B56","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13008-016-0021-6","article-title":"Insights into APC\/C: From cellular function to diseases and therapeutics","volume":"11","author":"Zhou","year":"2016","journal-title":"Cell Div"},{"issue":"3","key":"2022060319043402100_awab409-B57","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.neuron.2015.03.049","article-title":"A Cdh1-APC\/FMRP ubiquitin signaling link drives mGluR-dependent synaptic plasticity in the mammalian brain","volume":"86","author":"Huang","year":"2015","journal-title":"Neuron"},{"issue":"5","key":"2022060319043402100_awab409-B58","doi-asserted-by":"crossref","first-page":"101132","DOI":"10.1016\/j.isci.2020.101132","article-title":"Cdh1-APC regulates protein synthesis and stress granules in neurons through an FMRP-dependent mechanism","volume":"23","author":"Valdez-Sinon","year":"2020","journal-title":"iScience"},{"issue":"5","key":"2022060319043402100_awab409-B59","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/0092-8674(91)90397-H","article-title":"Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome","volume":"65","author":"Verkerk","year":"1991","journal-title":"Cell"},{"issue":"50","key":"2022060319043402100_awab409-B60","doi-asserted-by":"crossref","first-page":"35637","DOI":"10.1074\/jbc.M113.472076","article-title":"The HECT type ubiquitin ligase NEDL2 is degraded by anaphase-promoting complex\/cyclosome (APC\/C)-Cdh1, and its tight regulation maintains the metaphase to anaphase transition","volume":"288","author":"Lu","year":"2013","journal-title":"J Biol Chem"},{"issue":"2","key":"2022060319043402100_awab409-B61","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1136\/jmedgenet-2016-103943","article-title":"De novo missense variants in HECW2 are associated with neurodevelopmental delay and hypotonia","volume":"54","author":"Berko","year":"2017","journal-title":"J Med Genet"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awab409\/43488256\/awab409.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/145\/5\/1684\/43948410\/awab409.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/145\/5\/1684\/43948410\/awab409.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T12:58:40Z","timestamp":1726059520000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/145\/5\/1684\/6425675"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,11]]},"references-count":61,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,11,11]]},"published-print":{"date-parts":[[2022,6,3]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awab409","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.06.12.21256778","asserted-by":"object"}]},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,5,1]]},"published":{"date-parts":[[2021,11,11]]}}}