{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T17:19:56Z","timestamp":1780939196519,"version":"3.54.1"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Hum Genet"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>KDM2B<\/jats:italic>\n                    encodes an epigenetic regulator that binds to promoter-associated CpG islands\n                    <jats:italic>via<\/jats:italic>\n                    its CxxC zinc-finger domain, protecting them from DNA methylation. It also helps establish transcriptional programs essential for development by recruiting the non-canonical Polycomb Repressive Complex 1.1 to lineage-specific genes. Heterozygous variants in\n                    <jats:italic>KDM2B<\/jats:italic>\n                    were recently associated with a neurodevelopmental disorder. Notably, some individuals with variants in the CxxC domain also exhibited congenital heart, kidney and\/or structural eye anomalies. By screening 706 families with developmental eye disorders, we identified two cases with\n                    <jats:italic>KDM2B<\/jats:italic>\n                    -CxxC variants, NM_032590.5:c.1841G&gt;C;p.(Arg614Pro) and NM_032590.5:c.1880G&gt;C;p.(Cys627Ser), both resulting in a characteristic\n                    <jats:italic>KDM2B<\/jats:italic>\n                    DNA episignature. Both individuals exhibited complex structural eye defects, with neurodevelopmental, cardiac and renal anomalies variably present. These cases strengthen the association between\n                    <jats:italic>KDM2B<\/jats:italic>\n                    -CxxC variants and eye, kidney and heart malformations and highlight the importance of testing this gene and its episignature in individuals with structural eye disorders, especially when accompanied by congenital cardiac and\/or renal anomalies.\n                  <\/jats:p>","DOI":"10.1038\/s41431-026-02090-1","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T13:48:26Z","timestamp":1775569706000},"page":"874-879","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Variants in the CxxC domain of the epigenetic regulator KDM2B support its role in developmental eye anomalies"],"prefix":"10.1038","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7474-6361","authenticated-orcid":false,"given":"Fabiola","family":"Ceroni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5098-6336","authenticated-orcid":false,"given":"Linda M.","family":"Reis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Watkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorine A.","family":"Bax","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan C.","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthikah","family":"Jeganathan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9909-7142","authenticated-orcid":false,"given":"Rosalyn","family":"Jewell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5512-0929","authenticated-orcid":false,"given":"Jacob S.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Salt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Seese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Thomson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0531-3586","authenticated-orcid":false,"given":"Elena V.","family":"Semina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6122-4521","authenticated-orcid":false,"given":"Nicola K.","family":"Ragge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"2090_CR1","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1007\/s00439-018-1949-1","volume":"138","author":"A Slavotinek","year":"2019","unstructured":"Slavotinek A. Genetics of anophthalmia and microphthalmia. Part 2: syndromes associated with anophthalmia-microphthalmia. Hum Genet. 2019;138:831\u201346.","journal-title":"Hum Genet"},{"key":"2090_CR2","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.gim.2022.09.006","volume":"25","author":"RH van Jaarsveld","year":"2023","unstructured":"van Jaarsveld RH, Reilly J, Cornips MC, Hadders MA, Agolini E, Ahimaz P, et al. Delineation of a KDM2B-related neurodevelopmental disorder and its associated DNA methylation signature. Genet Med. 2023;25:49\u201362.","journal-title":"Genet Med"},{"key":"2090_CR3","doi-asserted-by":"crossref","unstructured":"van Oirsouw ASE, Hadders MA, Koetsier M, Peters EDJ, Assia Batzir N, Barakat TS, et al. KDM2B variants in the CxxC domain impair its DNA-binding ability and cause a distinct neurodevelopmental syndrome. 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Family 2 was recruited to the \u2018Genetics of Eye and Brain Anomalies\u2019 study (UK), approved by the Cambridge East Ethics Committee (REC 04\/Q0104\/129). Both studies are performed in accordance with the tenets of the Declaration of Helsinki. Written informed consent for publication of data and clinical images was provided by all participants\/legal guardians.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}