NF1 gene mutations in Japanese with neurofibromatosis 1 (NF1).

Neurofibromatosis 1 (NF1) is an autosomal dominant disease characterized by abnormalities in multiple tissues derived from the neural crest. We analysed 50 unrelated Japanese patients for NF1 mutations by using polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis for exons 28 to 36. Here, we demonstrate a single base pair (bp) insertional mutations in exon 31 in one patient (5843insA/5844insA/5845insA/5846insA) and a single adenine to guanine transitional mutation 4 bp upstream from the 3' end of intron 31 in two unrelated cases. The insertional mutation in exon 31 was novel and resulted in premature termination of the transcript. The other intron 31 mutations resulted in 4 bp insertions of cDNA between exon 31 and exon 32 with premature termination of the transcript, indicating that those transitions of intron 31 caused aberrant splice acceptor sites upstream from the 5' end of exon 32. However, as the same mutation of intron 31 has been reported previously in two cases of unrelated Caucasians, the splice junction mutation of intron 31 is thought to be common among different ethnic groups.