{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:29:34Z","timestamp":1790519374116,"version":"4.1.0"},"reference-count":25,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,4,4]],"date-time":"2019-04-04T00:00:00Z","timestamp":1554336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Young Academy Clinician\/Scientist program of Hannover Medical School","award":["n.a."],"award-info":[{"award-number":["n.a."]}]},{"DOI":"10.13039\/100015034","name":"Resist","doi-asserted-by":"publisher","award":["EXC 2155"],"award-info":[{"award-number":["EXC 2155"]}],"id":[{"id":"10.13039\/100015034","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Roesemarie-Germscheid foundation","award":["n.a."],"award-info":[{"award-number":["n.a."]}]},{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"publisher","award":["TTU 07.801"],"award-info":[{"award-number":["TTU 07.801"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Immunodeficiency, centromeric instability and facial anomalies syndrome 2 (ICF2) is a rare autosomal recessive primary immunodeficiency disorder. So far, 27 patients have been reported. Here, we present three siblings with ICF2 due to a homozygous ZBTB24 gene mutation (c.1222 T&gt;G, p. (Cys408Gly)). Immune deficiency in these patients ranged from late-onset combined immunodeficiency (CID) with severe respiratory tract infections and recurrent shingles to asymptomatic selective antibody deficiency. Evident clinical heterogeneity manifested despite a common genetic background, suggesting the pathogenic relevance of epigenetic modification. Immunological follow-up reveals a previously unidentified gradual depletion of B and CD4+ T cells in all three presented patients with transition of a common variable immunodeficiency (CVID)-like disease to late-onset-CID in one of them. Considering all previously published cases with ICF2, we identify inadequate antibody responses to vaccines and reduction in CD27+ memory B cells as prevalent immunological traits. High mortality among ICF2 patients (20%) together with the progressive course of immunodeficiency suggest that hematopoietic stem cell transplantation (HSCT) should be considered as a treatment option in due time.<\/jats:p>","DOI":"10.3390\/diseases7020034","type":"journal-article","created":{"date-parts":[[2019,4,4]],"date-time":"2019-04-04T11:31:57Z","timestamp":1554377517000},"page":"34","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Progressive Immunodeficiency with Gradual Depletion of B and CD4+ T Cells in Immunodeficiency, Centromeric Instability and Facial Anomalies Syndrome 2 (ICF2)"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0855-2945","authenticated-orcid":false,"given":"Georgios","family":"Sogkas","sequence":"first","affiliation":[{"name":"Department of Clinical Immunology and Rheumatology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Dubrowinskaja","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Rheumatology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke K.","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Lentes","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Ripperger","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mykola","family":"Fedchenko","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Ernst","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Rheumatology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7129-100X","authenticated-orcid":false,"given":"Alexandra","family":"Jablonka","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Rheumatology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Geffers","sequence":"additional","affiliation":[{"name":"Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Baumann","sequence":"additional","affiliation":[{"name":"Department of Paediatric Pulmonology, Allergy and Neonatology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhold E.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Rheumatology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faranaz","family":"Atschekzei","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Rheumatology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1080\/08916930802024202","article-title":"ICF, an immunodeficiency syndrome: DNA methyltransferase 3B involvement, chromosome anomalies, and gene dysregulation","volume":"41","author":"Ehrlich","year":"2008","journal-title":"Autoimmunity"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1002\/ajmg.a.31885","article-title":"ICF syndrome: High variability of the chromosomal phenotype and association with classical Hodgkin lymphoma","volume":"143A","author":"Schuetz","year":"2007","journal-title":"Am. 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