摘要
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.
出处
《中国临床医学》
北大核心
2005年第4期585-587,共3页
Chinese Journal of Clinical Medicine