{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:12:16Z","timestamp":1790017936964,"version":"4.0.1"},"reference-count":32,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS072129"],"award-info":[{"award-number":["R01 NS072129"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015326","name":"Common Fund","doi-asserted-by":"publisher","award":["U01HG007672"],"award-info":[{"award-number":["U01HG007672"]}],"id":[{"id":"10.13039\/100015326","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":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>HUWE1<\/jats:italic>\n                    (HECT, UBA, and WWE Domain Containing E3 Ubiquitin Protein Ligase1, OMIM 300697), located at Xp11.22, encodes a ubiquitin ligase that is highly conserved across species. Genetic variants in\n                    <jats:italic>HUWE1<\/jats:italic>\n                    described in multiple independent studies cause X\u2010linked intellectual disability, including in the patients identified by Juberg, Marsidi, and Brooks. This report describes 35 additional cases of individuals with variants in\n                    <jats:italic>HUWE1<\/jats:italic>\n                    and suggested guidelines for clinical management. Our study includes several female cases, which have not been widely reported previously. Our findings confirm earlier reported clinical features including developmental delay, autism, hypotonia, short stature, and dysmorphic facial features as well as additional multisystemic findings. Intrauterine growth restriction (IUGR) and feeding difficulties were common in the neonatal period. It is notable that nearly all females had\n                    <jats:italic>de novo<\/jats:italic>\n                    variants, and males had\n                    <jats:italic>de novo<\/jats:italic>\n                    or inherited variants from clinically unaffected carrier mothers. Three genetic hotspots were identified in evolutionarily conserved regions of HUWE1 that have clinical impact. This report provides additional characterization of the spectrum of HUWE1\u2010related neurodevelopmental disorder (HNDD).\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70127","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T04:50:51Z","timestamp":1776142251000},"page":"2010-2018","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["35 Individuals With\n                    <scp>HUWE1<\/scp>\n                    \u2010Related Neurodevelopmental Disorder and Suggested Clinical Evaluations"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5957-7918","authenticated-orcid":false,"given":"Mindy H.","family":"Li","sequence":"first","affiliation":[{"name":"Division of Genetics, Department of Pediatrics Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deziree L.","family":"Coleman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Department of Pharmacology University of Washington School of Medicine  Seattle Washington USA"},{"name":"Norcliffe Foundation Center for Integrative Brain Research, Seattle Children's Research Institute  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey","family":"Hogan","sequence":"additional","affiliation":[{"name":"Division of Genetics, Department of Pediatrics Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Luz","sequence":"additional","affiliation":[{"name":"Division of Genetics, Department of Pediatrics Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Bhandari","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8868-5891","authenticated-orcid":false,"given":"Newell","family":"Belnap","sequence":"additional","affiliation":[{"name":"Neurogenomics Division, Center for Rare Childhood Disorders, Translational Genomics Research Institute  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4454-1979","authenticated-orcid":false,"given":"Tiffany","family":"Busa","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Timone Children's Hospital, AP\u2010HM  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Coutton","sequence":"additional","affiliation":[{"name":"University Grenoble Alpes, Inserm, U1209, CHU Grenoble Alpes, Institut for Advanced Biosciences  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Dieterich","sequence":"additional","affiliation":[{"name":"University Grenoble Alpes, Inserm, U1209, CHU Grenoble Alpes, Institut for Advanced Biosciences  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Gorokhova","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Timone Children's Hospital, AP\u2010HM  Marseille France"},{"name":"Aix Marseille Univ INSERM, MMG, U 1251  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6254-5925","authenticated-orcid":false,"given":"Clara","family":"Hildebrandt","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism, Department of Pediatrics University of North Carolina, Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Logan","sequence":"additional","affiliation":[{"name":"Division of Neurosciences Children's Healthcare of Atlanta  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Mariani","sequence":"additional","affiliation":[{"name":"Department of Pediatrics ASST Lariana Sant'anna Hospital  Como Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7553-3245","authenticated-orcid":false,"given":"Manuela","family":"Morleo","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM)  Naples Italy"},{"name":"Department of Precision Medicine University of Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Nigro","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM)  Naples Italy"},{"name":"Department of Precision Medicine University of Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Pappas","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Clinical Genetics Services New York University Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4906-7428","authenticated-orcid":false,"given":"Rachel","family":"Rabin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Clinical Genetics Services New York University Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Schoch","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Selicorni","sequence":"additional","affiliation":[{"name":"Department of Pediatrics ASST Lariana Sant'anna Hospital  Como Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vandana","family":"Shashi","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Spillmann","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Tardy","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Timone Children's Hospital, AP\u2010HM  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha A. Schrier","family":"Vergano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Eastern Virginia Medical School, Children's Hospital of the King's Daughters  Norfolk Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0379-3267","authenticated-orcid":false,"given":"Brock","family":"Grill","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Department of Pharmacology University of Washington School of Medicine  Seattle Washington USA"},{"name":"Norcliffe Foundation Center for Integrative Brain Research, Seattle Children's Research Institute  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4157-2019","authenticated-orcid":false,"given":"Kristin","family":"Baranano","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2021.100240"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320510458"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5272\u201014.2015"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912874107"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.63959"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2004985"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/1235"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.4161\/23723548.2014.970048"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2014.05.014"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen\u20102015\u2010009537"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.06.010"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2007.11.002"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.007406"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13064\u2010020\u201000143\u20109"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589\u2010021\u201000831\u20105"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.7.2563"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.06.032"},{"issue":"5","key":"e_1_2_12_19_1","first-page":"714","article-title":"A New Form of X\u2010Linked Mental Retardation With Growth Retardation, Deafness, and Microgenitalism","volume":"32","author":"Juberg R. C.","year":"1980","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2021.01.012"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010017\u20100038\u20106"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.04.003"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.051805"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22844"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes13112023"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf4802"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2015.5"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0081791"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.555441"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1010941"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2019.02.002"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.07.009"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1727"}],"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.70127","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.70127","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70127","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:10:51Z","timestamp":1785834651000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.70127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,13]]},"references-count":32,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/ajmg.a.70127"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.70127","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,13]]},"assertion":[{"value":"2025-07-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}