Genomic organization and evolution of the NF1 microdeletion region.

Five to 10% of neurofibromatosis type 1 (NF1) individuals have a microdeletion (1.5 Mb) encompassing the entire NF1 region and neighboring genes. Microdeletion patients have a distinct phenotype with a more severe tumor burden. Most of the microdeletion breakpoints cluster in flanking paralogous regions (NF1REPs). We describe the complete genomic region covering the NF1 microdeletion and an extensive analysis of the genomic and transcriptional organization of the NF1REPs. The flanking NF1REPs have a total length of about 75 kb and are composed of several fragments. One of these fragments originated from chromosome 19 and contains a hot spot for microdeletion breakpoints. The analysis of the genomic organization of the NF1 microdeletion region and of the NF1REPs in particular is important for understanding the mechanism by which NF1 microdeletions are formed. This analysis will also help to identify loci potentially involved in the pathogenesis of the increased tumor load and malignancy risk observed in NF1 microdeletion patients.