{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:01:07Z","timestamp":1790388067620,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2021\u201002860"],"award-info":[{"award-number":["2021\u201002860"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006741","name":"Stiftelsen Frimurare Barnhuset i Stockholm","doi-asserted-by":"publisher","award":["51024"],"award-info":[{"award-number":["51024"]}],"id":[{"id":"10.13039\/501100006741","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pathogenic variants in the noncoding gene\n                    <jats:italic>RNU4\u20102<\/jats:italic>\n                    cause ReNU syndrome, a common neurodevelopmental disorder. Although the core phenotype is well described, longitudinal symptom progression and family perspectives remain insufficiently characterized. We identified 11 individuals with\n                    <jats:italic>RNU4\u20102<\/jats:italic>\n                    pathogenic variants through reanalysis of clinical whole genome sequencing (WGS) data from a previously undiagnosed cohort. Using deep phenotyping, including retrospective medical record review and parental insights, we delineated a recognizable age\u2010dependent clinical trajectory. Infancy was characterized by feeding difficulties, hypotonia, decelerating head growth, and visual abnormalities; early childhood by gait disturbances, autistic behavior, and seizure onset; and later childhood by persistent severe speech impairment with emerging orthopedic complications. Notably, feeding problems and seizures improved over time in several individuals. Core features included developmental delay, intellectual disability, speech abnormalities, hypotonia, autism, postnatal growth retardation, visual and brain abnormalities, and similar facial features. Parents emphasized strong social connectedness and affection and often described infancy as the most challenging stage due to feeding difficulties and failure to thrive. This study refines the natural history of ReNU syndrome and provides guidance for clinical management and counselling. It also highlights the value of routine WGS reanalysis as novel disease genes are identified.\n                  <\/jats:p>","DOI":"10.1111\/cge.70252","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:52:12Z","timestamp":1790387532000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deep Phenotyping in\n                    <scp>ReNU<\/scp>\n                    Syndrome Identifies a Recognizable Age\u2010Dependent Clinical Trajectory"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3648-971X","authenticated-orcid":false,"given":"Nadja","family":"Pekkola Pacheco","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics and Genomics Karolinska University Hospital  Stockholm Sweden"},{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malin","family":"Kvarnung","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Genomics Karolinska University Hospital  Stockholm Sweden"},{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Hammarsj\u00f6","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Genomics Karolinska University Hospital  Stockholm Sweden"},{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5831-385X","authenticated-orcid":false,"given":"Daniel","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Genomics Karolinska University Hospital  Stockholm Sweden"},{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8253-2507","authenticated-orcid":false,"given":"Bianca","family":"Tesi","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Genomics Karolinska University Hospital  Stockholm Sweden"},{"name":"Center for Hematology and Regenerative Medicine, Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britt Marie","family":"Anderlid","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Genomics Karolinska University Hospital  Stockholm Sweden"},{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9601-3137","authenticated-orcid":false,"given":"Giedre","family":"Grigelioniene","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Genomics Karolinska University Hospital  Stockholm Sweden"},{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Johansson Soller","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet  Stockholm Sweden"},{"name":"Department of Clinical Genetics Uppsala University Hospital  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7800-8665","authenticated-orcid":false,"given":"Liselot","family":"van der Laan","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Amsterdam UMC  Amsterdam the Netherlands"},{"name":"Amsterdam Reproduction &amp; Development Amsterdam UMC  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Willfors","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Genomics Karolinska University Hospital  Stockholm Sweden"},{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotta","family":"Ingvoldstad Malmgren","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Genomics Karolinska University Hospital  Stockholm Sweden"},{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0806-5602","authenticated-orcid":false,"given":"Anna","family":"Lindstrand","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Genomics Karolinska University Hospital  Stockholm Sweden"},{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommy","family":"St\u00f6dberg","sequence":"additional","affiliation":[{"name":"Neuropediatric Unit Karolinska Institutet  Stockholm Sweden"},{"name":"Neuropediatric Unit Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3285-4281","authenticated-orcid":false,"given":"Ann","family":"Nordgren","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Genomics Karolinska University Hospital  Stockholm Sweden"},{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet  Stockholm Sweden"},{"name":"Department of Clinical Genetics and Genomics Sahlgrenska University Hospital  Gothenburg Sweden"},{"name":"Institute of Biomedicine, University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica Maria","family":"Delgado\u2010Vega","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Genomics Karolinska University Hospital  Stockholm Sweden"},{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet  Stockholm 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