ON UNEQUAL ALLELIC EXPRESSION OF THE NEUROFIBROMIN GENE IN NEUROFIBROMATOSIS TYPE-1

The autosomal dominantly inherited disease neurofibromatosis type 1 (N F1) is caused by mutations of a large gene comprising 59 exons, which code for a protein with 2818 amino acids called neurofibromin, Employi ng an expressed polymorphic site in exon 5 of the neurofibromin gene, the expression of its alleles was analysed quantitatively by scanning radioactive RT-PCR fragments of this exon prepared from the RNA of fib roblast cell cultures from 15 NF1 patients and of white blood cells fr om one NF1 patient, Thirteen of the RNA preparations yielded unequal a mounts of the allelic messages, The deviations of the expression ratio s (A2:A1) from 1.0 ranged from -0.9 to +25.8, The allelic messages wer e equally represented in the RNA preparations from five informative he althy donors, Apart from fibroblasts this phenomenon could also be det ected in keratinocytes, melanocytes from normally pigmented skin and m elanocytes from a cafe-au-lait spot of one patient, Only one of three patients affected by stop mutations exhibited unequal allelic expressi on. When nuclear RNA from 10 of the 13 patients was examined, equal am ounts of the primary transcripts were found (average ratio A2/A1: 1.08 +/- 0.07 S.E.M.), indicating that unequal expression on the level of mRNA was not caused by mutations affecting transcriptional regulation, The ratio of the amount of neurofibromin to that of p120 GAP did not seem to be correlated with the extent of unequal allelic expression.