CAJ | 학술논문

目的探讨一个遗传性多巴反应性肌张力障碍(dopa-responsive dystonia,DRD)家系的临床特点及相关基因突变.方法收集一个DRD家系的临床资料及外周血样本,提取全基因组DNA,应用聚合酶链反应(PCR)及DNA直接测序方法进行三磷酸鸟苷环化酶-1(GCH-1)基因外显子突变检测.结果该家系患病成员临床特点方面个体差异较大,但所有患者均对左旋多巴制剂反应良好,且未见明显不良反应.基因分析显示5例患者及1例无症状直系亲属存在GCH-1基因第6号外显子上的缺失突变c.63 1_632delAT,引起框移突变.结论 DRD临床表现具有明显异质性,在同一家系不同患者之间存在较大差异,同一基因突变可引起不同的临床表现型,部分携带者可不发病.GCH-1基因第6号外显子上的缺失突变c.631_632delAT为DRD致病的遗传学基础之一.
목적 탐토일개유전성다파반응성기장력장애(dopa-responsive dystonia,DRD)가계적림상특점급상관기인돌변.방법 수집일개DRD가계적림상자료급외주혈양본,제취전기인조DNA,응용취합매련반응(PCR)급DNA직접측서방법진행삼린산조감배화매-1(GCH-1)기인외현자돌변검측.결과 해가계환병성원림상특점방면개체차이교대,단소유환자균대좌선다파제제반응량호,차미견명현불량반응.기인분석현시5례환자급1례무증상직계친속존재GCH-1기인제6호외현자상적결실돌변c.63 1_632delAT,인기광이돌변.결론 DRD림상표현구유명현이질성,재동일가계불동환자지간존재교대차이,동일기인돌변가인기불동적림상표현형,부분휴대자가불발병.GCH-1기인제6호외현자상적결실돌변c.631_632delAT위DRD치병적유전학기출지일.
Objective To evaluate the clinical features and guanosine triphosphate cyclohydrolase 1 (GCH-1) gene mutation in a family with dopa-responsive dystonia (DRD).Methods The clinical features of this family were collected and their peripheral blood samples were screened for mutation in GCH-1 gene using PCR and DNA direct sequencing.Results The clinical features among each patient in this family were different.But all affected family members had quite a good response to levodopa treatment without significant adverse reactions.DNA test showed an AT deletion mutation at point of 631-632 in the 6th exon of GCH-1 gene in 5 affected members and 1 asymptomatic immediate family member.Conclusions Clinical heterogeneity is an important characteristic of DRD and clinical symptoms vary intra-families.Same gene type may cause different phenotype and not all carriers are patients.The deletion mutation at point of 631-632 in the 6th exon of GCH-1 gene should be considered as a pathogenic mutation for DRD.