CAJ | 학술논문

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。
목적：대1례산발뇌건황류병환자적치병기인CYP27A1진행돌변감정。방법수집환자급부모적외주혈，제취기인조DNA，채용PCR확증CYP27A1기인적소유외현자급전절위점서렬，대PCR산물진행Sanger측서，동시대신발현적돌변재105명정상대조중진행측서，이배제다태성위점。결과환자적CYP27A1기인제2내함자발현1개전절위점돌변c.446+1G>T；제5외현자검측도2개착의돌변：c.877A>T(p.Met293Leu)급c.1016C>T (p.Thr339Met)。경측서험증，c.446+1G>T급c.877A>T(p.Met293Leu)래원우모친，위국내외상미보도적신돌변， c.1016C>T(p.Thr339Met)유전자부친，위일이지돌변。결론발현CYP27A1기인중2개신돌변c.446+1G>T、c.877A>T급1개이보도적돌변c.1016C>T，저일발현봉부료CYP27A1기인돌변보，위천명뇌건황류병적발병궤제제공신적수거。
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+1G>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.