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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

20卷

期数:

2014年05期

页码:

346-349

栏目:

基础医学

出版日期:

2014-09-20

文章信息/Info

Title:

Heterozygous exonic deletion of the GTP cyclohydrolase I gene in a Han Chinese dopa-responsive dystonia patients

文章编号:

1006-8147(2014)05-0346-04

作者:

李明珊¹; 蔡春友¹; 时文涛¹; 张本恕²; 李卫东¹

(1.天津医科大学基础医学研究中心,天津 300070;2.天津医科大学总医院神经内科,天津 300052)

Author(s):

LI Ming-shan¹;  CAI Chun-you¹;  SHI Wen-tao¹;  ZHANG Ben-shu²;  LI Wei-dong¹

(1.Research Center of Basic Medical Sciences, Tianjin Medical University,Tianjin 300070,China;2.Department of Neurology, General Hospital, Tianjin Medical University, Tianjin 300052, China)

关键词:

多巴反应性肌张力障碍; GTP环化水解酶I; 多重连接依赖式探针扩增; 实时定量PCR; 外显子缺失

Keywords:

dopa-responsive dystonia;  GTP cyclohydrolase 1;  multiple ligation-dependent probe amplification;  real time PCR;  exonic deletion

分类号:

R394.5

DOI:

-

文献标志码:

A

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；对于突变的散发性DRD患者，有必要检测GCH1基因缺失。

Abstract:

Objective: To investigate whether exonic deletions of GTP cyclohydrolase I (GCH1), Tyrosine hydroxylase (TH), and Epsilon-sarcoglycan Encoding (SGCE) genes account for the etiology of dopa-responsive dystonia 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.

参考文献/References:

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相似文献/References:

备注/Memo

备注/Memo:

基金项目 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（12JCZDJC 24700）
作者简介 李明珊(1987-)，女，硕士在读，研究方向：病理与病理生理学；

通信作者：李卫东，E-mail:liweidong98@hotmail.com。

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更新日期/Last Update: 2014-09-25