{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T10:24:19Z","timestamp":1789035859955,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,5,14]],"date-time":"2023-05-14T00:00:00Z","timestamp":1684022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["R21 MH131740"],"award-info":[{"award-number":["R21 MH131740"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["K23 HD102589"],"award-info":[{"award-number":["K23 HD102589"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["P30 HD071593"],"award-info":[{"award-number":["P30 HD071593"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["K23 NS119666"],"award-info":[{"award-number":["K23 NS119666"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Jansen\u2010de Vries syndrome (JdVS) is a neurodevelopmental condition attributed to pathogenic variants in Exons 5 and 6 of <jats:italic>PPM1D<\/jats:italic>. As the full phenotypic spectrum and natural history remain to be defined, we describe a large cohort of children and adults with JdVS. This is a retrospective cohort study of 37 individuals from 34 families with disease\u2010causing variants in <jats:italic>PPM1D<\/jats:italic> leading to JdVS. Clinical data were provided by treating physicians and\/or families. Of the 37 individuals, 27 were male and 10 female, with median age 8.75\u2009years (range 8\u2009months to 62\u2009years). Four families document autosomal dominant transmission, and 32\/34 probands were diagnosed via exome sequencing. The facial gestalt, including a broad forehead and broad mouth with a thin and tented upper lip, was most recognizable between 18 and 48\u2009months of age. Common manifestations included global developmental delay (35\/36, 97%), hypotonia (25\/34, 74%), short stature (14\/33, 42%), constipation (22\/31, 71%), and cyclic vomiting (6\/35, 17%). Distinctive personality traits include a hypersocial affect (21\/31, 68%) and moderate\u2010to\u2010severe anxiety (18\/28, 64%). In conclusion, JdVS is a clinically recognizable neurodevelopmental syndrome with a characteristic personality and distinctive facial features. The association of pathogenic variants in <jats:italic>PPM1D<\/jats:italic> with cyclic vomiting bears not only medical attention but also further pathogenic and mechanistic evaluation.<\/jats:p>","DOI":"10.1002\/ajmg.a.63226","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T06:35:46Z","timestamp":1684132546000},"page":"1900-1910","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["<scp>Jansen\u2010de Vries<\/scp> syndrome: Expansion of the <scp><i>PPM1D<\/i><\/scp> clinical and phenotypic spectrum in 34 families"],"prefix":"10.1002","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8162-5031","authenticated-orcid":false,"given":"Monica H.","family":"Wojcik","sequence":"first","affiliation":[{"name":"Division of Newborn Medicine, Department of Pediatrics and Harvard Medical School Boston Children's Hospital  Boston Massachusetts USA"},{"name":"Division of Genetics and Genomics, Department of Pediatrics and Harvard Medical School Boston Children's Hospital  Boston Massachusetts USA"},{"name":"Manton Center for Orphan Disease Research Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7008-1879","authenticated-orcid":false,"given":"Siddharth","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj B.","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Manton Center for Orphan Disease Research Boston Children's Hospital  Boston Massachusetts USA"},{"name":"Division of Neonatology, Department of Pediatrics, Miller School of Medicine University of Miami and Holtz Children's Hospital, Jackson Health System  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5409-8387","authenticated-orcid":false,"given":"Tugce B.","family":"Balci","sequence":"additional","affiliation":[{"name":"Medical Genetics Program of Southwestern Ontario London Health Sciences Centre  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9743-4205","authenticated-orcid":false,"given":"Bert","family":"Callewaert","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics, Pediatrics Department Ghent University Hospital  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Luigi","family":"Calvo","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology Unit Regina Margherita Children's Hospital, Azienda Ospedaliera\u2010Universitaria Citt\u00e0 della Salute e della Scienza  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5690-6504","authenticated-orcid":false,"given":"Diana","family":"Carli","sequence":"additional","affiliation":[{"name":"Department of Public Health and Pediatrics University of Torino  Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Caudle","sequence":"additional","affiliation":[{"name":"Medical Genetics Program of Southwestern Ontario London Health Sciences Centre  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Colaiacovo","sequence":"additional","affiliation":[{"name":"Medical Genetics Program of Southwestern Ontario London Health Sciences Centre  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3664-0707","authenticated-orcid":false,"given":"Laura","family":"Cross","sequence":"additional","affiliation":[{"name":"Clinical Genetics Children's Mercy Hospital  Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalliope","family":"Demetriou","sequence":"additional","affiliation":[{"name":"Centre for Clinical Genetics Sydney Children's Hospital  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katy","family":"Drazba","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center  Greenwood South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Dutra\u2010Clarke","sequence":"additional","affiliation":[{"name":"Division of Genetics, Department of Pediatrics, David Geffen School of Medicine University of California at Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Edwards","sequence":"additional","affiliation":[{"name":"Paediatrics, School of Medicine Western Sydney University, Hunter Genetics  Newcastle New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casie A.","family":"Genetti","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Department of Pediatrics and Harvard Medical School Boston Children's Hospital  Boston Massachusetts USA"},{"name":"Manton Center for Orphan Disease Research Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothy K.","family":"Grange","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomic Medicine Department of Pediatrics Washington University School of Medicine  St Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott E.","family":"Hickey","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Ohio State University College of Medicine, Division of Genetic &amp; Genomic Medicine, Nationwide Children's Hospital  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Isidor","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Nantes Hospital  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"K\u00fcry","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CHU Nantes, Service de G\u00e9n\u00e9tique M\u00e9dicale, Nantes, France; Nantes Universit\u00e9, CHU Nantes, CNRS, INSERM, L'institut du thorax  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert M.","family":"Lachman","sequence":"additional","affiliation":[{"name":"Departments of Behavioral Science, Medicine, and Psychiatry Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alinoe","family":"Lavillaureix","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique Clinique, Centre de R\u00e9f\u00e9rence Maladies Rares CLAD\u2010Ouest ERN ITHACA, CHU Rennes, H\u00f4pital Sud  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Lyons","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center  Greenwood South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Marcelis","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Donders Centre for Neuroscience Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elysa J.","family":"Marco","sequence":"additional","affiliation":[{"name":"Cortica Healthcare, Marin Center  San Rafael California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6776-6949","authenticated-orcid":false,"given":"Julian A.","family":"Martinez\u2010Agosto","sequence":"additional","affiliation":[{"name":"Division of Genetics, Departments of Pediatrics and Human Genetics, David Geffen School of Medicine University of California at Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Nowak","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Department of Pediatrics and Harvard Medical School Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Pizzol","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology Unit Regina Margherita Children's Hospital, Azienda Ospedaliera\u2010Universitaria Citt\u00e0 della Salute e della Scienza  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Planes","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique Clinique University Hospital Morvan  Brest France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eloise J.","family":"Prijoles","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center  Greenwood South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelise","family":"Riberi","sequence":"additional","affiliation":[{"name":"Department of Public Health and Pediatrics University of Torino  Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric T.","family":"Rush","sequence":"additional","affiliation":[{"name":"UKMC School of Medicine University of Missouri Kansas City  Kansas City Missouri USA"},{"name":"Division of Genetics, Children's Mercy Kansas City  Kansas City Missouri USA"},{"name":"Department of Internal Medicine University of Kansas School of Medicine  Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca E.","family":"Russell","sequence":"additional","affiliation":[{"name":"Division of Genetics, Departments of Pediatrics and Human Genetics, David Geffen School of Medicine University of California at Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rani","family":"Sachdev","sequence":"additional","affiliation":[{"name":"Centre for Clinical Genetics Sydney Children's Hospital  Sydney New South Wales Australia"},{"name":"School of Women's and Children's Health University of New South Wales  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betsy","family":"Schmalz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Ohio State University College of Medicine, Division of Genetic &amp; Genomic Medicine, Nationwide Children's Hospital  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Shears","sequence":"additional","affiliation":[{"name":"Oxford Centre for Genomic Medicine Oxford University Hospitals NHS Foundation Trust  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8601-0020","authenticated-orcid":false,"given":"David A.","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Wilson","sequence":"additional","affiliation":[{"name":"Oxford Centre for Genomic Medicine Oxford University Hospitals NHS Foundation Trust  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Jansen","sequence":"additional","affiliation":[{"name":"Donders Centre for Neuroscience Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0000-2917","authenticated-orcid":false,"given":"Bert B. A.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Donders Centre for Neuroscience Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia J.","family":"Curry","sequence":"additional","affiliation":[{"name":"Genetic Medicine, Department of Pediatrics University of California San Francisco\/Fresno  Fresno California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23203"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.06.009"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0288-4"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21062"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.5114\/pedm.2022.112861"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104892"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.02.005"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28198-8"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2019.02.007"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4352"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1120"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-019-0589-1"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-021-01242-6"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7610.2008.01887.x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nrl.2020.06.006"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26162"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62439"},{"key":"e_1_2_10_19_1","unstructured":"Pizzol A Adams K. A. Curry C. &Calvo P. L.(2022).Is cyclic vomiting syndrome part of Jansen de Vries syndrome? Abstract presented at: European Society for Pediatric Gastroenterology Hepatology and Nutrition 54th Annual Meeting June 22\u201325 2022."},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2018.05.006"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22844"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-15279-3"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2021.12.022"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0404-y"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.23480"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-02-769869"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63226","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T02:50:20Z","timestamp":1722394220000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63226"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,14]]},"references-count":25,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1002\/ajmg.a.63226"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63226","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,14]]},"assertion":[{"value":"2023-01-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}