Hatta N, Horiuchi T, Watanabe I, Kobayashi Y, Shirakata Y, Ohtsuka H, Minami T, Ueda K, Kokoroishi T, Fujita S
First Department of Internal Medicine, School of Medicine, Ehime University, Japan.
Biochem Biophys Res Commun. 1995 Jul 17;212(2):697-704. doi: 10.1006/bbrc.1995.2025.
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.
神经纤维瘤病1型（NF1）是一种常染色体显性疾病，其特征是源自神经嵴的多个组织出现异常。我们通过聚合酶链反应（PCR）-单链构象多态性（SSCP）分析对50名无亲缘关系的日本患者的第28至36外显子进行了NF1突变分析。在此，我们展示了1例患者外显子31中的单碱基对（bp）插入突变（5843insA/5844insA/5845insA/5846insA），以及2例无亲缘关系病例中位于内含子31 3'端上游4 bp处的单个腺嘌呤到鸟嘌呤的转换突变。外显子31中的插入突变是新发现的，导致转录本提前终止。其他内含子31突变导致外显子31和外显子32之间的cDNA插入4 bp并使转录本提前终止，这表明内含子31的那些转换导致了外显子32 5'端上游异常的剪接受体位点。然而，由于之前在2例无亲缘关系的高加索人中报道过相同的内含子31突变，因此内含子31的剪接连接突变被认为在不同种族群体中很常见。
