{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T23:17:12Z","timestamp":1789514232357,"version":"build-2803163510"},"reference-count":13,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare, autosomal recessive primary immunodeficiency, with fewer than 120 cases reported worldwide. ICF type 1 (ICF1) is the most prevalent subtype. Despite its rarity, ICF1 presents a distinct set of clinical features that necessitate increased awareness, particularly in populations with high rates of consanguinity. This case presents a two-year-old Palestinian boy born to consanguineous parents who presented with recurrent respiratory tract infections, facial dysmorphisms, and hypogammaglobulinemia. A comprehensive immunologic evaluation confirmed markedly reduced immunoglobulin levels consistent with an antibody deficiency. Genetic testing identified a homozygous missense mutation in\n                    <jats:italic>DNMT3B<\/jats:italic>\n                    (Arg826Cys), establishing the diagnosis. The patient was started on intravenous immunoglobulin (IVIG) replacement therapy, which was well tolerated and led to a noticeable reduction in infection frequency and an overall clinical well-being improvement. While treatment remains supportive, early recognition and immunologic management can significantly reduce morbidity. This case highlights the importance of early diagnosis and immunologic support in ICF1 syndrome, reinforces genotype\u2013phenotype correlations, and provides valuable insights from an underrepresented region to improve global awareness, diagnosis, and care, being only the second genetically confirmed case from Palestine.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1742293","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T05:38:10Z","timestamp":1768973890000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Epigenetic disruption meets immune deficiency: a case report of ICF syndrome linked to DNMT3B mutation"],"prefix":"10.3389","volume":"16","author":[{"given":"Zaid Al","family":"Ali","sequence":"first","affiliation":[{"name":"Medical Research Club, Faculty of Medicine, Al-Quds University","place":["Jerusalem, Palestine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled F.","family":"Al-Ali","sequence":"additional","affiliation":[{"name":"Medical Research Club, Faculty of Medicine, Al-Quds University","place":["Jerusalem, Palestine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Bader","sequence":"additional","affiliation":[{"name":"Medical Research Club, Faculty of Medicine, Al-Quds University","place":["Jerusalem, Palestine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Alhalabiya","sequence":"additional","affiliation":[{"name":"Medical Research Club, Faculty of Medicine, Al-Quds University","place":["Jerusalem, Palestine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deema","family":"Sous","sequence":"additional","affiliation":[{"name":"Department of pediatrics, An-Najah National University","place":["Ramallah, Palestine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayah","family":"Abulehia","sequence":"additional","affiliation":[{"name":"Medical Research Club, Faculty of Medicine, Al-Quds University","place":["Jerusalem, Palestine"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.18502\/ijaai.v20i2.6058","article-title":"Immunodeficiency, centromeric region instability, and facial anomalies syndrome (ICF) in a boy with variable clinical and immunological presentations","volume":"20","author":"Bemanian","year":"2021","journal-title":"Iranian J Allergy Asthma Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2174\/1871530320666200613204426","article-title":"Clinical, immunologic and molecular spectrum of patients with immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome: A systematic review","volume":"21","author":"Kiaee","year":"2020","journal-title":"Endocrine Metab Immune Disord - Drug Targets"},{"key":"B3","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1016\/j.ajhg.2011.04.018","article-title":"Mutations in ZBTB24 are associated with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2","volume":"88","author":"De Greef","year":"2011","journal-title":"Am J Hum Genet"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1042\/ebc20190035","article-title":"DNA methylation in disease: Immunodeficiency, Centromeric instability, Facial anomalies syndrome","volume":"63","author":"Vukic","year":"2019","journal-title":"Essays Biochem"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2018.00140","article-title":"DNMT3B functions: novel insights from human disease","volume":"6","author":"Gagliardi","year":"2018","journal-title":"Front Cell Dev Biol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/omcr\/omaf079","article-title":"Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome identified by whole-exome sequencing (WES): a case report from a developing country","volume":"6","author":"Joma","year":"2025","journal-title":"Oxford Med Case Rep"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1517417","article-title":"Case report: Novel multi-exon homozygous deletion of ZBTB24 causes immunodeficiency, centromeric instability, and facial anomalies syndrome 2","volume":"16","author":"Long","year":"2025","journal-title":"Front Immunol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"7870","DOI":"10.1038\/ncomms8870","article-title":"Mutations in CDCA7 and HELLS cause immunodeficiency\u2013centromeric instability\u2013facial anomalies syndrome","volume":"6","author":"Thijssen","year":"2015","journal-title":"Nat Commun"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-016-0240-2","article-title":"Genetic, cellular and clinical features of ICF syndrome: a french national survey","volume":"36","author":"Sterlin","year":"2016","journal-title":"J Clin Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-018-0569-9","article-title":"Three types of immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome identified by whole-exome sequencing in saudi hypogammaglobulinemia patients: clinical, molecular, and cytogenetic features","volume":"38","author":"Alghamdi","year":"2018","journal-title":"J Clin Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0578-1310.2019.01.013","article-title":"Clinical and genetic manifestations of immunodeficiency, centromeric instability, and facial anomalies syndrome: a case report and literature review","volume":"57","author":"Hu","year":"2019","journal-title":"Zhonghua er ke za zhi = Chin J Pediatr"},{"key":"B12","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1007\/s10875-024-01786-7","article-title":"Allogeneic hematopoietic stem cell transplantation in immunodeficiency\u2014Centromeric instability\u2014Facial dysmorphism (ICF) syndrome: an EBMT\/ESID inborn errors working party study","volume":"44","author":"Berghuis","year":"2024","journal-title":"J Clin Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/biom13121717","article-title":"ICF1-Syndrome-Associated DNMT3B Mutations Prevent De Novo Methylation at a Subset of Imprinted Loci during iPSC Reprogramming","volume":"13","author":"Verma","year":"2023","journal-title":"Biomolecules"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1742293\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T05:38:15Z","timestamp":1768973895000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1742293\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,21]]},"references-count":13,"alternative-id":["10.3389\/fimmu.2025.1742293"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1742293","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,21]]},"article-number":"1742293"}}