颅内海绵状血管瘤CCM1基因8号外显子基因突变的分析及704insT新插入突变位点

Analysis of CCM1 Gene 8 ^(th) Exon Mutation of Intracranial Cavernous Angiomas and A New 704insT Insertion Site

目的 分析国人颅内海绵状血管瘤(ICCA)CCM 1基因8号外显子基因突变的情况。方法 收集2 1例ICCA患者及30例正常健康人外周静脉血,进行DNA抽提、PCR扩增8号外显子后直接测序,并与GenBank比较。结果 1例ICCA患者8号外显子在相当于CCM 1基因第70 4、70 5位碱基G和A之间插入碱基T(70 4insT) ,产生移码效应,使得编码的KRIT1蛋白氨基酸序列在第2 4 6位出现终止密码子TAA ,肽链合成提前终止。其余检测均无异常。结论 国人ICCA患者8号外显子存在CCM 1基因的突变,新发现的8号外显子70 4insT插入突变导致编码的KRIT1蛋白功能缺失,与ICCA发病有关。

Purpose To analyse mutations of CCM1 gene ,8 th exon of Chinese intracranial cavernous angiomas(ICCAs). Methods The peripheral venous blood of 21 ICCA patients and 30 healthy individuals were recruited,from which DNAs were extracted and 8 th exons were amplified by PCR.The PCR products were sequenced directly an d the results were compared with GenBank. Results In one patient,a new insertion frameshift muta tion 704insT of CCM1 gene 8 th exon was found between 704G and 705A,which caused a terminal codon T in the No.246 codon of KRIT1 protein appearing and the syn thesis of KRIT1 peptide chains stopped earlier.Other patients and healthy indiv iduals were normal. Conclusions There were mutations in CCM1 gene 8 th exon of Chinese ICCAs.The 704insT insertion mutation newly found caused KRIT1 p rotein′s function losing and was related to the occurring of ICCA.