In an effort to define the clinical and immunologic phenotype of IPEX and to explore a possible phenotype-genotype correlation, we have evaluated more than 100 patients from over 60 families who presented with the clinical phenotype of IPEX for mutations in FOXP3. To date, we have identified over 30 novel mutations, including missense mutations in the proline-rich domain, the leucine zipper, and the forkhead domain in addition to deletions and splice-site mutations. In one family with multiple affected members, we found a large deletion upstream of exon 1 resulting in failure to initiate normal splicing. Two families were found to have a point mutation affecting the first canonical polyadenylation region (Bennett et al. 2001). In our experience, only 60% of patients presenting with the IPEX phenotype have identifiable mutation of FOXP3.
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