Molecular analysis of the 5 '-flanking region of the neurofibromatosis type 1 (NF1) gene: identification of five sequence variants

Dideoxy fingerprinting was used to analyse the 5' flanking region of the ne urofibromin (NF1) gene in a panel of 380 neurofibromatosis type 1 (NF1) pat ients. Five polymorphisms/rare variants were identified at positions -412, -402, +16, +25 and +132, but control data indicated that these were unlikel y to be of pathological significance. Promoter mutations in the NF1 gene are not, therefore, a common cause of NF 1. This notwithstanding, a reporter gene assay was per formed to determine if these variants could affect the expression of the NF1 gene, and all thre e changes in the 5'-untranslated region (UTR) (+16, +25, +132) were found t o be associated with a 60-70% increase in reporter gene expression.