杂合子导致CADASIL病患者家系NOTCH3基因突变  

NOTCH 3 heterozygous mutation causing cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in a Chinese family

作　　者：王雪[1,2] 杨昆 韩涛[1] 李文娜[1] 位坤坤[1] 刘奇迹[2] 刘学伍[1] 

机构地区：[1]山东大学齐鲁医院神经内科,济南250012 [2]山东大学医学院医学遗传学研究所,济南250012 [3]山东省枣庄市山亭区人民医院神经内科,山东枣庄277200

出　　处：《山东大学学报（医学版）》2012年第9期63-67,共5页Journal of Shandong University:Health Sciences

摘　　要：目的研究一伴皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病(CADASIL)患者家系NOTCH3基因突变,探讨突变分析方法在遗传性CADASIL疾病筛查和诊断中的应用。方法收集该家系8位成员(5例患者,3例正常个体)外周血标本,提取基因组DNA。采用PCR扩增NOTCH3基因突变热点区域,DNA直接测序检测扩增产物,寻找该家系致病的突变基因。结果 NOTCH3基因第4外显子内存在一杂合的错义突变(c.421C>T),导致141位精氨酸(Arg)被半胱氨酸(Cys)替代。该家系中患者均携带该突变基因,而家系中正常个体未发现此突变基因。结论杂合的错义突变(c.421C>T)与该CADASIL家系中患者表型共分离,为引起该家系的致病基因突变。Objective To analyse the NOTCH3 mutation of patients in a large Chinese family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy（CADASIL）,and to discuss the application of mutation detection in the screening and diagnosis of genetic disease CADASIL.Methods Peripheral blood of 8 individuals（5 patients with CADASIL,3 normal individuals） was collected and the genomic DNA was extracted.Polymerase chain reaction（PCR） was performed for the hot spot mutation region amplification of NOTCH3.Direct DNA sequencing was used to find the pathologic mutation of the family with CADASIL.Results A heterozygous missense mutation in exon 4 of NOTCH3 gene（c.421CT）was found,causing arginine at 141 position replaced by cysteine.The patients with CADASIL all carried this mutation,whereas the normal individuals did not.Conclusion The heterozygous missense mutation（c.421CT） is co-segregation with the phenotype of the individuals with CADASIL in the Chinese family,which is the disease-causing mutation for the family.

关 键 词：CADASIL病 基因 NOTCH3 点突变 基因诊断 脑血管意外 

分 类 号：R743.9[医药卫生—神经病学与精神病学]