一例脑腱黄瘤病患者的CYP27A1基因突变  

Mutation analysis of CYP27A1 gene in a patient with cerebrotendinous xanthomatosis

作　　者：钟诚[1] 赵强[1] 邓佳[1] 王一鸣[1] 胡彬[1] 李洵桦[2] 

机构地区：[1]中山大学中山医学院医学遗传学教研室,广州510080 [2]中山大学附属第一医院神经科

出　　处：《中国神经精神疾病杂志》2014年第1期2-6,共5页Chinese Journal of Nervous and Mental Diseases

基　　金：国家自然科学基金(编号:81171070)

摘　　要：目的对1例散发脑腱黄瘤病患者的致病基因CYP27A1进行突变鉴定。方法收集患者及父母的外周血,提取基因组DNA,采用PCR扩增CYP27A1基因的所有外显子及剪切位点序列,对PCR产物进行Sanger测序,同时对新发现的突变在105名正常对照中进行测序,以排除多态性位点。结果患者的CYP27A1基因第2内含子发现1个剪切位点突变c.446+1G>T;第5外显子检测到2个错义突变:c.877A>T(p.Met293Leu)及c.1016C>T(p.Thr339Met)。经测序验证,c.446+1G>T及c.877A>T(p.Met293Leu)来源于母亲,为国内外尚未报道的新突变,c.1016C>T(p.Thr339Met)遗传自父亲,为一已知突变。结论发现CYP27A1基因中2个新突变c.446+1G>T、c.877A>T及1个已报道的突变c.1016C>T,这一发现丰富了CYP27A1基因突变谱,为阐明脑腱黄瘤病的发病机制提供新的数据。Objective To investigate the causative mutations of CYP27A1 gene in a sporadic cerebrotendinous xanthomatosis patient. Methods Genomic DNA was extracted from peripheral blood of the patient and her parents. All exons and splice sites of CYP27A1 gene were amplified by polymerase chain reaction （PCR） followed by Sanger sequenc-ing. 105 healthy unrelated subjects were also sequenced for the novel mutation in CYP27A1. Results A novel splice site mutation c.446＋lG〉T, a novel missense mutation c.877A〉T（p.Met293Leu） and a known missense mutation c.1016C〉T （p.Thr339Met） of CYP27A1 gene were identified in the patient. The mother carriers the two novel mutations and the fa-ther the c.1016C〉T（p.Thr339Met） mutation. The two novel mutations were absent in 105 control subjects, respectively. Conclusions Our study detected two novel mutations, c.446 ＋ 1G〉T and c.877A〉T, as well as a known mutation c.1016C〉T, of CYP27A1 in a sporadic cerebrotendinous xanthomatosis patient. Our data provide novel information for the mutational spectrum of the gene, which is applicable in the genetic testing and diagnosis. The data also provide in-sight into the pathogenesis of the disease.

关 键 词：脑腱黄瘤病 CYP27A1基因 突变 

分 类 号：R739.41[医药卫生—肿瘤]