SCANNING THE FIRST PART OF THE NEUROFIBROMATOSIS TYPE-1 GENE BY RNA-SSCP - IDENTIFICATION OF 3 NOVEL MUTATIONS AND OF 2 NEW POLYMORPHISMS

Neurofibromatosis type 1 (NF1) of von Recklinghausen is a common autos omal dominant disorder, characterized by peripheral neurofibromas, caf e-au-lait spots and Lisch nodules of the iris. The high mutation rate at the NF1 locus results in a wide range of molecular abnormalities. W e have scanned 14 different exons from the first part of the NF1 gene using the RNA-single strand conformation polymorphism (RNA-SSCP) metho d in a series of 40 NF1 patients. Three novel mutations, two nonsense and one missense, and two polymorphisms have been detected in familial cases. Genotype-phenotype correlations have been investigated, but no particular association has been detected. After this screening, the m ajority of NF1 chromosomes has not yet been characterized, confirming the difficulty in detecting the defect underlying NF1 in most families , even following extensive DNA analysis.