Sunday 19 March 2006
Definition: Autosomal-recessive immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is mainly characterized by recurrent, often fatal, respiratory and gastrointestinal infections.
About 50% of patients carry mutations in the DNA methyltransferase 3B gene (DNMT3B) (ICF1).
- germline mutations of ZBTB24 in ICF2 syndrome (ZBTB24)
- The remaining patients carry unknown genetic defects (ICF2) but share with ICF1 patients the same immunological and epigenetic features, including hypomethylation of juxtacentromeric repeat sequences.
- ZBTB24 is involved in DNA methylation of juxtacentromeric DNA and in B cell development and/or B and T cell interactions.
- ZBTB24 is a putative DNA-binding protein highly expressed in the lymphoid lineage.
height Below the third percentile
weight Below the third percentile
head circumference below the third percentile
failure to thrive
low set ears
flat nasal bridge
small upturned nose
variable mental retardation ranging from severe neurodegeneration to mild mental retardation
Reduced number of T cells
Reduced number of natural killer cells
Centromeric instability of chromosomes 1, 9 and 16 with increased somatic recombination and formation of multibranched configurations
germline mutations of DNMT3 in ICF syndrome
Mutations in ZBTB24 are associated with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2. de Greef JC, Wang J, Balog J, den Dunnen JT, Frants RR, Straasheijm KR, Aytekin C, van der Burg M, Duprez L, Ferster A, Gennery AR, Gimelli G, Reisli I, Schuetz C, Schulz A, Smeets DF, Sznajer Y, Wijmenga C, van Eggermond MC, van Ostaijen-Ten Dam MM, Lankester AC, van Tol MJ, van den Elsen PJ, Weemaes CM, van der Maarel SM. Am J Hum Genet. 2011 Jun 10;88(6):796-804. PMID: #21596365#