一个新的胆固醇酯转运蛋白基因移码突变的鉴定

Identification of a novel frame shift mutation of cholesteryl ester transfer protein gene

收集在脂质专科门诊就诊者中血清高密度脂蛋白－胆固醇（ＨＤＬ－Ｃ）高于１．８０ｍｍｏｌ／Ｌ的全血标本，通过聚合酶链反应（ＰＣＲ）技术扩增胆固醇酯转运蛋白（ＣＥＴＰ）基因，继而采用荧光直读法进行ＣＥＴＰ基因组ＤＮＡ序列分析，发现一女性先驱者为ＣＥＴＰ基因新的移码突变杂合子，即ＣＥＴＰ第３８位密码子中胞嘧啶碱基的缺失引起阅读框架的改变，致使第４８位密码子变为提前的转录终止信号。从该基因变异的性质和该先驱者的血脂变化（ＨＤＬ－Ｃ２．５１ｍｍｏｌ／Ｌ）提示该基因突变为一ＣＥＴＰ合成缺陷的无义突变。

The whole blood samples were collected from individuals who visited the lipid clinic and whose HDL C levels were over 1.80 mmol/L. The human genomic DNA of cholesteryl ester transfer protein(CETP) was amplified with polymerase chain reaction(PCR) and was sequencedly using automated laser fluorescence technique. It was identified that a female heterozygote proband who carries a novel frame shift mutation of CETP gene, ie. the deletion of cytocine in codon 38 leads to the totally variation of reading frame and the premature stop signal in codon 48. According to the nature of this genetic variant and serum lipid profile(HDL C 2.51 mmol/L) of this proband, it is suggested that the frame shift variation might be nonsense mutation of CETP gene which results in CETP synthesis deficiency.