title: Heterogeneous clinical presentation in ICF syndrome: correlation with underlying gene defects.
abstract: Immunodeficiency with centromeric instability and facial anomalies (ICF) syndrome is a primary immunodeficiency, predominantly characterized by agammaglobulinemia or hypoimmunoglobulinemia, centromere instability and facial anomalies. Mutations in two genes have been discovered to cause ICF syndrome: DNMT3B and ZBTB24. To characterize the clinical features of this syndrome, as well as genotype-phenotype correlations, we compared clinical and genetic data of 44 ICF patients. Of them, 23 had mutations in DNMT3B (ICF1), 13 patients had mutations in ZBTB24 (ICF2), whereas for 8 patients, the gene defect has not yet been identified (ICFX). While at first sight these patients share the same immunological, morphological and epigenetic hallmarks of the disease, systematic evaluation of all reported informative cases shows that: (1) the humoral immunodeficiency is generally more pronounced in ICF1 patients, (2) B- and T-cell compartments are both involved in ICF1 and ICF2, (3) ICF2 patients have a significantly higher incidence of intellectual disability and (4) congenital malformations can be observed in some ICF1 and ICF2 cases. It is expected that these observations on prevalence and clinical presentation will facilitate mutation-screening strategies and help in diagnostic counseling.
authors.affiliation: Department of Pediatric Infectious Diseases and Immunology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Corry M R
authors.initials: CM
authors.lastname: Weemaes
authors.forename: Maarten J D
authors.initials: MJ
authors.lastname: van Tol
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Monique M
authors.initials: MM
authors.lastname: van Ostaijen-ten Dam
authors.forename: Marja C J A
authors.initials: MC
authors.lastname: van Eggermond
authors.forename: Peter E
authors.initials: PE
authors.lastname: Thijssen
authors.forename: Caner
authors.initials: C
authors.lastname: Aytekin
authors.forename: Nicola
authors.initials: N
authors.lastname: Brunetti-Pierri
authors.forename: Mirjam
authors.initials: M
authors.lastname: van der Burg
authors.forename: E
authors.initials: E
authors.lastname: Graham Davies
authors.forename: Alina
authors.initials: A
authors.lastname: Ferster
authors.forename: Dieter
authors.initials: D
authors.lastname: Furthner
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gimelli
authors.forename: Andy
authors.initials: A
authors.lastname: Gennery
authors.forename: Barbara
authors.initials: B
authors.lastname: Kloeckener-Gruissem
authors.forename: Stephan
authors.initials: S
authors.lastname: Meyn
authors.forename: Cynthia
authors.initials: C
authors.lastname: Powell
authors.forename: Ismail
authors.initials: I
authors.lastname: Reisli
authors.forename: Catharina
authors.initials: C
authors.lastname: Schuetz
authors.forename: Ansgar
authors.initials: A
authors.lastname: Schulz
authors.forename: Andrea
authors.initials: A
authors.lastname: Shugar
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van den Elsen
authors.forename: Silvère M
authors.initials: SM
authors.lastname: van der Maarel
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D003710:Demography; D005145:Face / Q000002:abnormalities*; D005260:Female; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007153:Immunologic Deficiency Syndromes / Q000097:blood / Q000235:genetics* / Q000628:therapy; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D000081207:Primary Immunodeficiency Diseases; D012097:Repressor Proteins / Q000235:genetics*; D055815:Young Adult; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D007074:Immunoglobulin G; D012097:Repressor Proteins; D000097584:DNA Methyltransferase 3B; C560314:ZBTB24 protein, human