2型神经纤维瘤病NF2基因的突变分析

Mutation Analysis of NF2 Gene in a Chinese Neurofibromatosis lype 2 Kindred

目的:探讨中国人常染色体显性遗传2型神经纤维瘤病的基因突变和分子诊断。方法:应用基因测序和限制性片段长度多态性分析技术,对1例经临床与病理诊断为2型神经纤维瘤病家系及100名无血缘关系正常人NF2基因编码区的17个外显子及其邻近内含子序列进行突变检测和分析。结果:家系中的所有患病者存在内含子13剪接供体位点(1446+1位)g→a的杂合性碱基点突变,而正常人和家系中未患病者无此突变,并排除了该位点基因多态性的可能。结论:该突变为国内外新发现的NF2基因内含子13剪接供体位点突变,突变导致的剪接异常影响了Merlin蛋白的生物学功能,使其失去对正常神经细胞生长的调控,导致2型神经纤维瘤病的发生。

Objective： To elucidate the molecular mechanism of neurofibromatosis type 2 （NF2） with autosomal dominant inheritance disease in a Chinese kindred. Methods： The entire coding region （from exon 1 through 17） of the NF2 gene was amplified using Polymerase chain reaction （PCR） and evaluated for mutations using direct sequencing of the PCR products. PCR-restriction fragment length posymorphism （PCR-RFLP） was performed to exclude the possibility of NF2 polymorphism in 100 normal control individuals. Results： The clinical and pathologic features including electron microscope examination established the diagnosis of NF2. A novel point mutation （1446 ＋ 1 g→a） at the boundary of exon 13 and intron 13 was identified, which leads to an altered splice donor site and aberrant coding DNA sequence. Condusion：The de novo splice donor point mutation in intron 13 of NF2 gene which causes the production of a substantially truncated protein is related to the tumorigenesis of NF2.