{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:24:53Z","timestamp":1760145893813,"version":"build-2065373602"},"reference-count":5,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The etiology of neurodevelopmental disorders and epilepsy is very heterogeneous and partly still unknown, and the research of causative genes related to these diseases is still in progress. In 2020, pathogenic variants of the TET3 gene were associated with Beck\u2013Fahrner syndrome, which is characterized by neurodevelopmental delay, intellectual and learning disabilities of variable degree, growth abnormalities, hypotonia and seizures. Variants of TET3 have been described having both an autosomal dominant with a milder phenotype and an autosomal recessive pattern. To date, in the literature, only 28 patients are reported with pathogenic variants of the TET3 gene, and only 9 of them have epilepsy. We describe a 31-year-old woman with macrocephaly, mild neurodevelopmental delay and a long history of epilepsy. Trio-based exome sequencing identified a de novo heterozygous TET3 variant, c.2867G&gt;A p.(Arg956Gln), never described before, absent in the general population and predicted to be potentially pathogenetic by bioinformatics tools. This report aims to describe the clinical history of our patient, the pharmacological treatment and clinical response, as well as the biological characteristics of this new variant.<\/jats:p>","DOI":"10.3390\/ijms25179676","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T10:29:45Z","timestamp":1725618585000},"page":"9676","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A New De Novo Missense Variant of the TET3 Gene in a Patient with Epilepsy and Macrocephaly"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0335-5862","authenticated-orcid":false,"given":"Miryam Rosa Stella","family":"Foti","sequence":"first","affiliation":[{"name":"Unit\u00e0 di Genetica Medica, Azienda Ospedaliera Sant\u2019Anna, Dip. Scienze Mediche e Dip. Materno-Infantile, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4790-6573","authenticated-orcid":false,"given":"Maria Giovanna","family":"Tedesco","sequence":"additional","affiliation":[{"name":"Istituto Malattie Rare \u201cMauro Baschirotto\u201d, Costozza di Longare, 36100 Vicenza, Italy"},{"name":"UOSD Genetica Medica e Malattie Rare, Dip. Materno-Infantile, Azienda Ospedaliera di Perugia, 06129 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide","family":"Colavito","sequence":"additional","affiliation":[{"name":"Research & Innovation (R&I Genetics) Srl, 35100 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Rogaia","sequence":"additional","affiliation":[{"name":"UOSD Genetica Medica e Malattie Rare, Dip. Materno-Infantile, Azienda Ospedaliera di Perugia, 06129 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amedea","family":"Mencarelli","sequence":"additional","affiliation":[{"name":"UOSD Genetica Medica e Malattie Rare, Dip. Materno-Infantile, Azienda Ospedaliera di Perugia, 06129 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Schippa","sequence":"additional","affiliation":[{"name":"UOSD Genetica Medica e Malattie Rare, Dip. Materno-Infantile, Azienda Ospedaliera di Perugia, 06129 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Gradassi","sequence":"additional","affiliation":[{"name":"UOSD Genetica Medica e Malattie Rare, Dip. Materno-Infantile, Azienda Ospedaliera di Perugia, 06129 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2612-9796","authenticated-orcid":false,"given":"Rita","family":"Romani","sequence":"additional","affiliation":[{"name":"UOSD Genetica Medica e Malattie Rare, Dip. Materno-Infantile, Azienda Ospedaliera di Perugia, 06129 Perugia, Italy"},{"name":"Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmela","family":"Ardisia","sequence":"additional","affiliation":[{"name":"UOSD Genetica Medica e Malattie Rare, Dip. Materno-Infantile, Azienda Ospedaliera di Perugia, 06129 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Prontera","sequence":"additional","affiliation":[{"name":"UOSD Genetica Medica e Malattie Rare, Dip. Materno-Infantile, Azienda Ospedaliera di Perugia, 06129 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.ajhg.2019.12.007","article-title":"Delineation of a Human Mendelian Disorder of the DNA Demethylation Machinery: TET3 Deficiency","volume":"106","author":"Beck","year":"2020","journal-title":"Am. Soc. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.braindev.2022.09.004","article-title":"A novel de novo TET3 loss-of-function variant in a Turkish boy presenting with neurodevelopmental delay and electrical status epilepticus during slow-wave sleep","volume":"45","author":"Sager","year":"2023","journal-title":"Brain Dev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s10038-021-00986-y","article-title":"Two families with TET3-related disorder showing neurodevelopmental delay with craniofacial dysmorphisms","volume":"67","author":"Seyama","year":"2022","journal-title":"J. Hum. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1038\/s41431-019-0385-6","article-title":"Schilbach\u2013Rott syndrome associated with 9q22.32q22.33 duplication, involving the PTCH1 gene","volume":"27","author":"Prontera","year":"2019","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_5","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., and Amemiya, A. (2023). TET3-Related Beck-Fahrner Syndrome Synonyms: TET3-BEFAHRS, TET3 Deficiency. GeneReviews, University of Washington."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/17\/9676\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:49:58Z","timestamp":1760111398000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/17\/9676"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,6]]},"references-count":5,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ijms25179676"],"URL":"https:\/\/doi.org\/10.3390\/ijms25179676","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2024,9,6]]}}}