title: Combined immunodeficiency develops with age in Immunodeficiency-centromeric instability-facial anomalies syndrome 2 (ICF2).
abstract: The autosomal recessive immunodeficiency-centromeric instability-facial anomalies syndrome (ICF) is characterized by immunodeficiency, developmental delay, and facial anomalies. ICF2, caused by biallelic ZBTB24 gene mutations, is acknowledged primarily as an isolated B-cell defect. Here, we extend the phenotype spectrum by describing, in particular, for the first time the development of a combined immune defect throughout the disease course as well as putative autoimmune phenomena such as granulomatous hepatitis and nephritis. We also demonstrate impaired cell-proliferation and increased cell death of immune and non-immune cells as well as data suggesting a chromosome separation defect in addition to the known chromosome condensation defect.
authors.affiliation: Pediatric Pneumology and Immunology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. horst.von-bernuth@charite.de.|Labor Berlin Charité Vivantes GmbH, Department of Immunology, Berlin, Germany. horst.von-bernuth@charite.de.
authors.forename: Horst
authors.initials: H
authors.lastname: von Bernuth
authors.affiliation: Institute of Cell Biology and Neurobiology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. ethiraj.ravindran@charite.de.|Pediatric Neurology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. ethiraj.ravindran@charite.de.
authors.forename: Ethiraj
authors.initials: E
authors.lastname: Ravindran
authors.affiliation: Berlin Institute for Medical Systems Biology, Max-Delbrueck-Center for Molecular Medicine, Robert-Rössle-Str. 10, 13092, Berlin, Germany. hang.du@mdc-berlin.de.
authors.forename: Hang
authors.initials: H
authors.lastname: Du
authors.affiliation: Berlin Institute for Medical Systems Biology, Max-Delbrueck-Center for Molecular Medicine, Robert-Rössle-Str. 10, 13092, Berlin, Germany. sebastian.froehler@mdc-berlin.de.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Fröhler
authors.affiliation: Pediatric Pneumology and Immunology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. karoline.strehl@charite.de.
authors.forename: Karoline
authors.initials: K
authors.lastname: Strehl
authors.affiliation: Institute of Cell Biology and Neurobiology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. nadine.kraemer@charite.de.|Pediatric Neurology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. nadine.kraemer@charite.de.
authors.forename: Nadine
authors.initials: N
authors.lastname: Krämer
authors.affiliation: Institute of Cell Biology and Neurobiology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. ina.jahns@charite.de.|Pediatric Neurology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. ina.jahns@charite.de.
authors.forename: Lina
authors.initials: L
authors.lastname: Issa-Jahns
authors.affiliation: Max Planck Institute for Infection Biology, Berlin, Germany. amulic@mpiib-berlin.mpg.de.
authors.forename: Borko
authors.initials: B
authors.lastname: Amulic
authors.affiliation: Institute of Cell Biology and Neurobiology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. olaf.ninnemann@charite.de.
authors.forename: Olaf
authors.initials: O
authors.lastname: Ninnemann
authors.affiliation: Berlin Institute for Medical Systems Biology, Max-Delbrueck-Center for Molecular Medicine, Robert-Rössle-Str. 10, 13092, Berlin, Germany. mei-sheng.xiao@mdc-berlin.de.
authors.forename: Mei-Sheng
authors.initials: MS
authors.lastname: Xiao
authors.affiliation: Institute for Human Genetics, Biozentrum, Universität Würzburg, Würzburg, Germany. katharina.eirich@uni-wuerzburg.de.
authors.forename: Katharina
authors.initials: K
authors.lastname: Eirich
authors.affiliation: Labor Berlin Charité Vivantes GmbH, Department of Immunology, Berlin, Germany. uwe.koelsch@charite.de.
authors.forename: Uwe
authors.initials: U
authors.lastname: Kölsch
authors.affiliation: Institute for Pathology, Charité - Universitätsmedizin Berlin, Berlin, Germany. kathrin.hauptmann@charite.de.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Hauptmann
authors.affiliation: Pediatric Neurology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. rainer.john@charite.de.
authors.forename: Rainer
authors.initials: R
authors.lastname: John
authors.affiliation: Institute for Human Genetics, Biozentrum, Universität Würzburg, Würzburg, Germany. schindler@biozentrum.uni-wuerzburg.de.
authors.forename: Detlev
authors.initials: D
authors.lastname: Schindler
authors.affiliation: Pediatric Pneumology and Immunology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. volker.wahn@charite.de.
authors.forename: Volker
authors.initials: V
authors.lastname: Wahn
authors.affiliation: Berlin Institute for Medical Systems Biology, Max-Delbrueck-Center for Molecular Medicine, Robert-Rössle-Str. 10, 13092, Berlin, Germany. wei.chen@mdc-berlin.de.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Institute of Cell Biology and Neurobiology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. angela.kaindl@charite.de.|Pediatric Neurology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. angela.kaindl@charite.de.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Kaindl
mesh_terms: D001327:Autoimmune Diseases / Q000175:diagnosis / Q000235:genetics; D002503:Centromere / Q000235:genetics*; D002648:Child; D043171:Chromosomal Instability / Q000235:genetics*; D002877:Chromosomes, Human / Q000235:genetics; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005145:Face / Q000002:abnormalities*; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis* / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D000081207:Primary Immunodeficiency Diseases; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: D012097:Repressor Proteins; C560314:ZBTB24 protein, human