2 RECURRENT NONSENSE MUTATIONS AND A 4-BP DELETION IN A QUASI-SYMMETRICAL ELEMENT IN EXON-37 OF THE NF1 GENE

We screened a total of 92 unrelated patients with neurofibromatosis ty pe 1 (NF1) for mutations in exon 37 of the NF1 gene, by using temperat ure gradient gel electrophoresis. Two novel mutations were found: a 4 bp deletion in a so-called quasi-symmetric element (6789del-TTAC) and a recurrent nonsense mutation, which was identified in two unrelated p atients, at codon 2264 (C6792A). The independent origin of the latter mutation in two families was confirmed by haplotype analysis. The nons ense mutation and the 4 bp deletion are both predicted to lead to a tr uncated protein product lacking the C-terminal 20% (aproximately) of i ts sequence. The occurrence of three independent mutations among 92 NF 1 patients at codons 2263-2264 (exon 37) suggests that a specific sear ch for mutations in this area should be undertaken in screening progra ms for NF1 mutations.