{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T02:13:25Z","timestamp":1783649605216,"version":"3.55.0"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T00:00:00Z","timestamp":1707177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>UPF3B<\/jats:italic> encodes the Regulator of nonsense transcripts 3B protein, a core\u2010member of the nonsense\u2010mediated mRNA decay pathway, protecting the cells from the potentially deleterious actions of transcripts with premature termination codons. Hemizygous variants in the <jats:italic>UPF3B<\/jats:italic> gene cause a spectrum of neuropsychiatric issues including intellectual disability, autism spectrum disorder, attention deficit hyperactivity disorder, and schizophrenia\/childhood\u2010onset schizophrenia (COS). The number of patients reported to date is very limited, often lacking an extensive phenotypical and neuroradiological description of this ultra\u2010rare syndrome. Here we report three subjects harboring <jats:italic>UPF3B<\/jats:italic> variants, presenting with variable clinical pictures, including cognitive impairment, central hypotonia, and syndromic features. Patients 1 and 2 harbored novel <jats:italic>UPF3B<\/jats:italic> variants\u2014the p.(Lys207*) and p.(Asp429Serfs*27) ones, respectively\u2014while the p.(Arg225Lysfs*229) variant, identified in Patient 3, was already reported in the literature. Novel features in our patients are represented by microcephaly, midface hypoplasia, and brain malformations. Then, we reviewed pertinent literature and compared previously reported subjects to our cases, providing possible insights into genotype\u2013phenotype correlations in this emerging condition. Overall, the detailed phenotypic description of three patients carrying <jats:italic>UPF3B<\/jats:italic> variants is useful not only to expand the genotypic and phenotypic spectrum of <jats:italic>UPF3B<\/jats:italic>\u2010related disorders, but also to ameliorate the clinical management of affected individuals.<\/jats:p>","DOI":"10.1002\/ajmg.a.63534","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T09:20:50Z","timestamp":1707297650000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Expanding the phenotype of <scp><i>UPF3B<\/i><\/scp>\u2010related disorder: <scp>Case<\/scp> reports and literature review"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3933-0597","authenticated-orcid":false,"given":"Ferruccio","family":"Romano","sequence":"first","affiliation":[{"name":"Clinical Genomics and Genetics Unit IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria K.","family":"Haanp\u00e4\u00e4","sequence":"additional","affiliation":[{"name":"Department of Genomics and Clinical Genetics Turku University Hospital  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawel","family":"Pomianowski","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics and Genomics Christiana Care Health System  Newark Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda Rose","family":"Peraino","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics and Genomics Christiana Care Health System  Newark Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Pollard","sequence":"additional","affiliation":[{"name":"Epilepsy Center Christiana Care Health System  Newark Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria 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