Tuesday 20 December 2011
germline mutations in ICF2 syndrome
- 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).
- 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.
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