Ten novel mutations in the human neurofibromatosis type 1 (NF1) gene in Italian patients.

The entire NF1 coding region was analyzed for mutations in a panel of 108 unrelated Italian NF1 patients. Using PTT, SSCP, and DNA sequencing, we found 10 mutations which have never been reported before. Clinical diagnosis of NF1 was established according to the NIH consensus criteria in 100 individuals, while 8 were young children with only multiple cafè-au-lait spots. We detected 46 truncated fragments, and 24 of them were fully characterized by SSCP and direct sequencing. Of the 24, 14 were known mutations (R304X, R681X, Q682X, R1306X, R1362X, R1513X, R1748X, Q1794X, R1947X, Y2264X, R2237X, 2674delA, 6789delTTAC, 2027insC). The other 10 mutations represent novel changes that contribute to the germline mutational spectrum of the NF1 gene (K810X, Q2595X, 6772delT, 7190delCT, 7331delA, 1021insTT, 3921insT, 4106insTA, 7149insC, 2033insCG / 2034delA). PTT in a large number of Italian NF1 patients supports the usefulness of this method for characterization of mutations in disorders where the responsible gene is very large and the disease-causing mutations often create a stop codon. In agreement with previous reports, no mutational hotspots within the NF1 gene were detected.