CHARACTERIZATION AND SIGNIFICANCE OF 9 NOVEL MUTATIONS IN EXON-16 OF THE NEUROFIBROMATOSIS TYPE-1 (NF1) GENE

Nine novel mutations have been characterized as the result of screenin g exon 16 of the human NF1 gene in 465 unrelated neurofibromatosis typ e 1 patients. These lesions include three nonsense and two missense mu tations, two deletions, one duplication, and one mutation in the 5' sp lice site of intron 16. Although exon 16 is the largest NF1 exon, no m utations have so far been reported in this region. This apparent pauci ty of lesions may be due either to a reduced functional importance of exon 16 or a screening bias or both. However, consideration of the mut ability of exon 16 in comparison with other exons suggests that, at le ast for single base pair substitutions, no such factors need be invoke d. Any previous lack of exon 16 mutations in this category would be ex plicable in terms of a lower propensity to mutate for codons in this g ene region.