结节性硬化症双生子中TSC2基因突变的检测

目的:对一对结节性硬化症双生子患者及其父母候选基因的突变进行检测,揭示该病的遗传基础。方法:采用聚合酶链式反应,扩增结节性硬化症双生子患者TSC2基因的全部外显子,以及内含子外显子交接区,进行DNA直接测序分析;利用限制性片段长度多态性(RFLP)技术检测了患者的父母和500个健康人的突变,并分析本突变是否和结节性硬化症有关。结果:双生子患者中均发现一个TSC2基因的错义突变c.G2032A,该突变导致TSC2蛋白678位的丙氨酸被替换为苏氨酸(p.A678T);RFLP结果显示患者的父亲有c.G2032A突变,500个正常人中有3人也携带此突变。结论:在结节性硬化症人群中发现TSC2基因新的突变,这一发现丰富了该基因引起结节性硬化症的突变谱。

Identification of TSC2 Mutation in Twin Patients with Tuberous Sclerosis Complex

Objective：To identify gene mutations in twin patients with tuberous sclerosis com-plex（ TSC） and their parents .Methods：All the coding region , including all exons and exon-in-tron boundaries of TSC 2 were amplified by polymerase chain reaction .The products were analyzed by direct DNA sequencing .The gene of their parents and 500 unrelated healthy Chinese individuals were analysed by RFLP （ restriction fragment length polymorphism ） to search for the mutation and to test whether the mutation co-segregates with the disease .Results：One nucleotide G in 2032 TSC2 was substituted by A , which caused a missense mutation p .A678 T in both of the twin pa-tients.RFLP results showed that their father and three of the 500 normal individuals carried the c . G2032A mutation.Conclusion：A novel missense mutation p .A678T was identified in Chinese pa-tients with Tuberous Sclerosis Complex , which expand the mutation spectrum of TSC 2 mutations which showed the correlation with TSC .