摘要
目的:基于对汉族人群中的多巴反应性肌张力障碍(DRD)患者基因突变的研究,进一步探究GTP环化水解酶I基因(GCH1)、酪氨酸羟化酶基因(TH)、Epsilon-sarcoglycan编码基因(SGCE)上是否存在外显子缺失。方法:对来自4个DRD家系共8名患者及其5名无症状家属、10名散发性DRD患者和3名正常对照者的GCH1、TH、SGCE基因的22个外显子进行多重连接式探针扩增(MLPA)分析,对MLPA结果出现异常的外显子采用实时定量PCR(qPCR)进行验证,然后使用ddCt法与正常对照者比较分析GCH1、TH、SGCE基因是否存在外显子缺失。结果:1名散发性DRD患者的GCH1基因1号外显子出现杂合缺失,正常对照均未发现此外显子缺失。其余家系或散发性患者未检测到外显子缺失或扩增。结论:在汉族人群中,散发性DRD患者GCH1基因存在外显子缺失,但出现频率较低;对于突变阴性的散发性DRD患者,有必要检测其GCH1基因是否存在缺失。
Objective： To investigate whether exonic deletions of GTP cyclohydrolase Ⅰ（GCH1）, Tyrosine hydroxylase （TH）, and Epsilonsarcoglycan Encoding （SGCE） genes account for the etiology of dopa-responsive dystonia （I）RD） in Han Chinese patients. Methods： The blood samples were collected from 26 subjects： 8 patients and 5 healthy family members in four pedigrees, 10 sporadic patients, and 3 unrelated normal individuals. Multiple ligation-dependent probe amplification analysis was performed on 22 exons of 3 genes （GCH1, TH, and SGCE） to detect plausible deletions. To confirm the MLPA results, quantitative real-time PCR was applied to candidate exons, and the comparative threshold cycle method （ddCt） was used to detect exonic deletions of GCH1, TH, SGCE genes. Results： A GCH1 exon 1 heterozygous deletion was detected in a sporadic DRD patient while no other deletions/duplications were observed in family or sporadic samples. Conclusion： Exonic deletion of GCH1 may contribute to certain DRD cases, but it is relatively rare; It is necessary to detect exonic deletions in the DRD cases if no genetic mutation is found.
出处
《天津医科大学学报》
2014年第5期346-349,共4页
Journal of Tianjin Medical University
基金
国家自然科学基金资助项目(81070576)
天津市自然科学基金重点项目(12JCZDJC24700)
