Exon 10b of the NF1 gene represents a mutational hotspot and harbors a recurrent missense mutation Y489C associated with aberrant splicing

Purpose: To analyze the spectrum and frequency of NF1 mutations in exon 10b . Methods: Mutation and sequence analysis was performed at the DNA and cDNA level. Results: We identified nine exon 10b mutations in 232 unrelated pat ients. Some mutations were recurrent (Y489C and L508P), others were unique (1465-1466insC and IVS10b + 2delTAAG). Surprisingly, at the RNA level, Y489 C causes skipping of the last 62 nucleotides of exon 10b. Another recurrent mutation, L508P, is undetectable by the Protein Truncation Test. Conclusio n: As exon 10b shows the highest mutation rate yet found in any of the 60 N F1 exons, it should be implemented with priority in mutation analysis.