LOCALIZATION OF THE ICF SYNDROME TO CHROMOSOME-20 BY HOMOZYGOSITY MAPPING

Immunodeficiency in association with centromere instability of chromos omes 1, 9, and 16 and facial anomalies (ICF syndrome) is a rare autoso mal recessive disorder. ICF patients show marked hypomethylation of th eir DNA; undermethylation of classical satellites II and III is though t to be associated with the centromere instability. We used DNA from t hree consanguineous families with a total of four ICF patients and per formed a total genome screen, to localize the ICF syndrome gene by hom ozygosity mapping. One chromosomal region (20q11-q13) was consistently found to be homozygous in ICF patients, whereas all healthy sibs show ed a heterozygous pattern. Comparison of the regions of homozygosity i n the four ICF patients localized the ICF locus to a 9-cM region betwe en the markers D20S477 and D20S850. Analysis of more families will be required, to refine the map location further. Isolation of the gene as sociated with the ICF syndrome not only will give insight into the eti ology of the ICF syndrome but will also broaden our understanding of D NA methylation processes.