{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:22:08Z","timestamp":1791339728136,"version":"4.3.1"},"reference-count":15,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T00:00:00Z","timestamp":1777075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>The WW domain-containing oxidoreductase (WWOX) gene, well-known as a tumor suppressor, also has a crucial role as a transcription factor in the developing brain. The bi-allelic loss of the WWOX gene causes a condition characterized by drug-resistant epilepsy, developmental delay, and neurological impairments, often resulting in mortality within the first year of life, known as WWOX-related epileptic encephalopathy (WOREE) syndrome (MIM: 616211). Whole Exome Sequencing (WES) analysis was performed on a female patient who died within three months of birth and was diagnosed with microcephaly, severe early-onset refractory seizures, and drug-resistant epileptic encephalopathy. WES revealed a 38 kb CNV deletion spanning WWOX exons 6\u20137, and a known frameshift variant in exon 8, impairing a highly clinically significant region of the encoded protein. Clinical and genetic features of reported WOREE patients with WWOX gene deletions similar to our patient were analyzed. Our case highlights the clinical heterogeneity of WWOX variants in WOREE syndrome and expands the spectrum of reported compound heterozygous deletions. Further research needs to elucidate WWOX pathophysiology and improve diagnostic and therapeutic strategies.<\/jats:p>","DOI":"10.3390\/cimb48050449","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:09:33Z","timestamp":1777388973000},"page":"449","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["WWOX-Related Epileptic Encephalopathy (WOREE Syndrome): Clinical Case Study and Literature Review"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9433-026X","authenticated-orcid":false,"given":"Annamaria","family":"Sapuppo","sequence":"first","affiliation":[{"name":"Unit of Pediatrics and Pediatric Emergency Department, Azienda Ospedaliero-Universitaria Policlinico \u201cRodolico-San Marco\u201d, San Marco Hospital, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia","family":"Fusto","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Rocca","sequence":"additional","affiliation":[{"name":"Postgraduate Training Program in Pediatrics, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0188-8430","authenticated-orcid":false,"given":"Vincenzo","family":"Sortino","sequence":"additional","affiliation":[{"name":"Unit of Catania, Institute for Research and Biomedical Innovation (IRIB), National Council of Research, 95126 Catania, Italy"},{"name":"PhD Program in Innovative Technologies in Biomedical Sciences, University Kore of Enna, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xena Giada","family":"Pappalardo","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, 95123 Catania, Italy"},{"name":"Unit of Catania, Institute for Research and Biomedical Innovation (IRIB), National Council of Research, 95126 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martino","family":"Ruggieri","sequence":"additional","affiliation":[{"name":"Unit of Clinical Pediatrics and Unit of Rare Disease AOU \u201cPoliclinico\u201d, PO \u201cG. Rodolico\u201d, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4482-3506","authenticated-orcid":false,"given":"Raffaele","family":"Falsaperla","sequence":"additional","affiliation":[{"name":"Department of Medical Science-Pediatrics, University of Ferrara, 44124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1002\/gcc.22693","article-title":"WWOX, the FRA16D gene: A target of and a contributor to genomic instability","volume":"58","author":"Hussain","year":"2019","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Banne, E., Abudiab, B., Abu-Swai, S., Repudi, S.R., Steinberg, D.J., Shatleh, D., Alshammery, S., Lisowski, L., Gold, W., and Carlen, P.L. (2021). 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