CAJ | 학술논문

目的对1个多巴反应性肌张力障碍(dopa-responsive dystonia,DRD)家系成员的三磷酸鸟苷环化水解酶Ⅰ (guanosine triphosphate cyclohydrolase Ⅰ,GCH1)基因进行分析,以期找到致病基因突变.方法应用PCR扩增DRD家系成员的GCH1基因6个外显子及侧翼序列,产物直接进行序列测定.检测到的突变以变性高效液相色谱分析方法进行检测,寻找合适的洗脱条件,并且在100个正常人进行筛查,以排除突变为多态位点的可能.结果家系中所有患者均在GCH1基因第5外显子检测到一个碱基缺失突变c.597delT(p.Ala200LeufsX5),此突变国际上未见报道.突变将导致开放阅读框前移,自200位密码子开始出现移码突变,到第204位密码子即出现终止密码,使得正常为750个氨基酸残基的酶截短为203个氨基酸残基.100名正常人未见如患者类似的洗脱峰.结论研究明确了导致该DRD家系的基因异常,并且发现了一种新的GCH1基因突变.
목적 대1개다파반응성기장력장애(dopa-responsive dystonia,DRD)가계성원적삼린산조감배화수해매Ⅰ (guanosine triphosphate cyclohydrolase Ⅰ,GCH1)기인진행분석,이기조도치병기인돌변.방법 응용PCR확증DRD가계성원적GCH1기인6개외현자급측익서렬,산물직접진행서렬측정.검측도적돌변이변성고효액상색보분석방법진행검측,심조합괄적세탈조건,병차재100개정상인진행사사,이배제돌변위다태위점적가능.결과 가계중소유환자균재GCH1기인제5외현자검측도일개감기결실돌변c.597delT(p.Ala200LeufsX5),차돌변국제상미견보도.돌변장도치개방열독광전이,자200위밀마자개시출현이마돌변,도제204위밀마자즉출현종지밀마,사득정상위750개안기산잔기적매절단위203개안기산잔기.100명정상인미견여환자유사적세탈봉.결론 연구명학료도치해DRD가계적기인이상,병차발현료일충신적GCH1기인돌변.
Objective To identify potential mutation of the GCH1 gene in a Chinese family affected with dopa-responsive dystonia.Methods Genomic DNA of patients was extracted from peripheral blood samples.The 6 exons of the GCH1 gene and at least 100 bp of flanking intronic sequences were amplified with PCR.Potential mutations were screened by direct sequencing.Identified mutation was verified with denaturing high performance liquid chromatography (DHPLC) in 100 healthy controls.Results All patients were found to be heterozygous for a novel c.597delT (p.Ala200LeufsX5) deletion in the exon 5 of the GCH1 gene.The deletion of T has resulted in formation of a shorter (203 amino acids) truncated non-functional guanosine triphosphate cyclohydrolase I.The same mutation was not found in the 100 controls.Conclusion A novel GCH1 gene frameshifing mutation probably underlies the dopa-responsive dystonia in this Chinese family.