ICF (Immunodefieciency, Centromeric instability, Facial anomalies) syndrome (OMIM 242860) is a rare autosomal recessive disorder. Hallmark features are recurrent infections at an early age, unstable chromosomes in white blood cells and hypomethylation of satellite 2 and 3 DNA. Facial anomalies of varying degrees are frequently observed and intellectual disability is not uncommon. About 50% of the ICF patients show an association with a mutation in the gene DNMT3B encoding a methyl transferase that is thought to play a role during de novo methylation. We have investigated the DNA from two different ICF patients. While both show the typical chromosomal rearrangements and the hypomethylation pattern, we were not able to find a mutation in any of the coding exons of DNMT3B, nor in the promoter region. A candidate gene approach, sequencing of genes encoding proteins of known interaction with the methyl transferase, has not yet revealed a causative mutation. Currently, we are analyzing comparative genome hybridization (array CGH) experiments from genomic DNA of one of the two ICF patients, conducted in collaboration with Ralph Schlapbach from the Functional Genomics Center Zurich (FGCZ).
We do offer genetic testing for ICF syndrome by (1) chromosomal analysis. In case of a positive cytogenetic diagnosis, we will (2) sequence all coding exons of DNMT3B. Please refer to our genetic testing pages for more information on requirements for DNA diagnostics. Genetic Testing
Wolfgang Berger (PhD)
Barbara Kloeckener (PhD)
David Betts, National Center for Medical Genetics, Dublin, Ireland
Tayfun Güngör (MD), Childrens Hospital of the University of Zurich, Switzerland