{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:46:46Z","timestamp":1787503606619,"version":"build-2736575974"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2025,9]]},"abstract":"ABSTRACT<\/jats:title>\n \n Nonsense\u2010mediated mRNA decay (NMD) plays a crucial role in degrading aberrant transcripts with premature termination codons, with the Up\u2010frameshift (UPF) protein family\u2014UPF1, UPF2, and UPF3A\/UPF3B\u2014being vital components of this machinery. While several variants in genes encoding UPF2 and UPF3A\/3B have been associated with neurodevelopmental disorders, only three germline\n UPF1<\/jats:italic>\n variants have been reported to date. Here, we report a male patient with a de novo missense variant, p.(Ala526Thr), in a highly conserved helicase motif of UPF1. The patient presented with moderate intellectual disability (ID), atypical autism, attention deficit hyperactivity disorder (ADHD), and behavioral disturbances. The common features observed among the four patients with\n UPF1<\/jats:italic>\n variants are moderate to severe ID and developmental delays in motor and verbal skills. A comparison across the disorders related to the UPF genes suggests that neurodevelopmental delay, including ID and impaired verbal skills, is a common feature, and these disorders may collectively be referred to as\n UPF<\/jats:italic>\n \u2010related neurodevelopmental disorders (NDDs). ADHD, autism, seizures, hypotonia, and non\u2010specific dysmorphic features are also reported in some patients, suggesting that these disorders can be classified as non\u2010specific intellectual disability syndromes. However, further studies are necessary to elucidate genotype\u2013phenotype correlations and the molecular mechanisms underlying these rare disorders, particularly those related to UPF1.\n <\/jats:p>","DOI":"10.1111\/cge.14735","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T04:08:42Z","timestamp":1740542922000},"page":"313-317","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Novel\n \n UPF1<\/i>\n <\/scp>\n Variant Associated With a Rare\n \n UPF1<\/i>\n <\/scp>\n \u2010Related Neurodevelopmental Disorder"],"prefix":"10.1111","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4777-5802","authenticated-orcid":false,"given":"Zeynep","family":"T\u00fcmer","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics Copenhagen University Hospital, Rigshospitalet Copenhagen Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Dalsberg","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Copenhagen University Hospital, Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gitte","family":"R\u00f8nde","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Copenhagen University Hospital, Herlev and Gentofte Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7735-4622","authenticated-orcid":false,"given":"Jesper Kiehn","family":"S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Copenhagen University Hospital, Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsebet","family":"\u00d8stergaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Copenhagen University Hospital, Rigshospitalet Copenhagen Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20763"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2020.08.010"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0148191"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.4.814"},{"key":"e_1_2_10_6_1","first-page":"665","article-title":"Gene Variants Involved in Nonsense\u2010Mediated mRNA Decay Suggest a Role in Autism Spectrum Disorder","volume":"10","author":"Marques A. 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