变性高压液相色谱分析在中国家族性CADASIL患者基因筛查中的应用  

Application of Denaturing High Performance Liquid Chromatography in Genetic Diagnosis in Chinese Patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

作　　者：唐晓梅[1] 陈彪[1] 

机构地区：[1]首都医科大学宣武医院老年病研究所

出　　处：《神经损伤与功能重建》2008年第3期156-160,共5页Neural Injury and Functional Reconstruction

基　　金：国家863计划(No.2001AA227051)

摘　　要：目的:探讨变性高压液相色谱分析(DHPLC)在伴皮质下梗死及白质脑病的常染色体显性遗传性脑动脉病(CADASIL)患者诊断中的方法和价值。方法:运用DHPLC及DNA直接测序技术,对CADASIL家系先证者、家系成员14例(CADASIL组)及健康对照者100例(对照组)进行Notch3基因检测。结果:CADASIL组发现3种致病性突变,其中Cys134Tyr为新的突变类型,同时发现15种多态类型;对照组中未发现突变。结论:DHPLC技术在筛查Notch3中起重要作用,但在筛查时应进行多个柱温的测试,温度调换以2℃为宜。Objective： To observe the significance of denaturing high performance liquid chromatography （DHPLC） in genetic diagnosis in chinese patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy （CADASIL）. Methods： DHPLC and DNA sequencing were used to identify the pathogenetic mutations in Notch3 gene in 4 probands and 10 family members from 3 unrelated Chinese CADASIL families and 100 healthy controls. Results： Three heterozygous missense mutations in exons 3 and 4 were found among the families but not in 200 chromosomes of controls. The Cys134Tyr was a novel mutation that has not been reported previously. There were also 15 polyrnorphisms found. Conclusion： DHPLC was a sensitive method to screen for mutations in Notch3 gene, but attention should be paid to optimize the oven temperature with the fluctuation of two degrees.

关 键 词：变性高压液相色谱分析 伴皮质下梗死及白质脑病的常染色体显性遗传性脑动脉病 NOTCH3 突变 

分 类 号：R741[医药卫生—神经病学与精神病学] R743.9[医药卫生—临床医学]