{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T15:57:55Z","timestamp":1785772675465,"version":"3.56.0"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The 2p15p16.1 microdeletion syndrome is a rare neurodevelopmental disorder caused by heterozygous deletions of variable size involving multiple dosage\u2010sensitive genes. Within the narrowed critical interval,\n                    <jats:italic>USP34<\/jats:italic>\n                    has emerged as a particularly strong candidate for the core phenotype, supported by reports of smaller deletions involving only\n                    <jats:italic>USP34<\/jats:italic>\n                    and\n                    <jats:italic>XPO1<\/jats:italic>\n                    , and by the fact that\n                    <jats:italic>USP34<\/jats:italic>\n                    encodes a deubiquitinating enzyme that stabilizes Axin and thereby regulates canonical Wnt\/\u03b2\u2010catenin signaling, a pathway critical for neurodevelopment, craniofacial morphogenesis, and limb patterning. We report six individuals with heterozygous loss\u2010of\u2010function variants in\n                    <jats:italic>USP34<\/jats:italic>\n                    , including five with confirmed de novo variants, associated with global developmental delay, craniofacial dysmorphism, marked speech impairment, variable autism spectrum disorder, and distal limb anomalies. The phenotype associated with isolated loss of\n                    <jats:italic>USP34<\/jats:italic>\n                    overlaps substantially with that reported in 2p15p16.1 microdeletion syndrome, while suggesting that some features seen in larger deletions may reflect the contribution of additional genes within the interval. These findings support haploinsufficiency of USP34 as sufficient to cause a distinct neurodevelopmental disorder, establish\n                    <jats:italic>USP34<\/jats:italic>\n                    as a major contributor to the neurodevelopmental and dysmorphic phenotype associated with the 2p15p16.1 locus, and refine gene\u2010specific contributions within this microdeletion syndrome.\n                  <\/jats:p>","DOI":"10.1111\/cge.70194","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T23:40:20Z","timestamp":1781826020000},"page":"315-324","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>USP34<\/scp>\n                    Haploinsufficiency as a Cause of Neurodevelopmental Phenotypes"],"prefix":"10.1111","volume":"110","author":[{"given":"Helena","family":"Wigoda","sequence":"first","affiliation":[{"name":"Department of Pediatrics Center for Precision Medicine University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8534-7921","authenticated-orcid":false,"given":"Amjad","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Zoology Institute of Biological Sciences, University of Lakki Marwat  Lakki Marwat Khyber Pakhtunkhwa Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8174-5116","authenticated-orcid":false,"given":"Bryce A.","family":"Mendelsohn","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kaiser Permanente Oakland Medical Center  Oakland California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Miyake","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Nagasaki University Institute of Biomedical Sciences  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Osaka Women's and Children's Hospital  Izumi Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9846-6500","authenticated-orcid":false,"given":"Naomichi","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Graduate School of Medicine, Yokohama City University  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia J. C.","family":"Knijnenburg","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Amsterdam UMC  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna M.","family":"van Hagen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Amsterdam UMC  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiddeke","family":"van de Kamp","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Amsterdam UMC  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quinten","family":"Waisfisz","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Amsterdam UMC  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6174-4677","authenticated-orcid":false,"given":"Bryn D.","family":"Webb","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Center for Precision Medicine University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38302"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.85461"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13258\u2010023\u201001369\u20107"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2025.101555"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010024\u201001701\u2010z"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2014.05.008"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/cga.12112"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/cga.12119"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238\u2010014\u20100019\u20102"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01094\u201010"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2021.764756"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11689\u2010016\u20109176\u20103"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102308\u20107"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22844"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.12.015"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.045013"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.2147\/TACG.S465575"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3180\u201006.2006"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0012\u20101606(03)00123\u20104"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201899398"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70194","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.70194","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70194","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T15:31:20Z","timestamp":1785771080000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.70194"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,18]]},"references-count":20,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/cge.70194"],"URL":"https:\/\/doi.org\/10.1111\/cge.70194","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,18]]},"assertion":[{"value":"2026-05-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}