遗传 ›› 2015, Vol. 37 ›› Issue (8): 731-740.doi: 10.16288/j.yczz.15-033

• 综述 •    下一篇

特发性基底节钙化致病的分子机制

王程1,徐旋1,李璐璐1,王涛2,张旻3,沈璐4,唐北沙4,刘静宇1   

  1. 1. 华中科技大学生命科学与技术学院,分子生物物理教育部重点实验室,武汉430074;
    2. 华中科技大学同济医学院附属协和医院神经内科,武汉430022;
    3. 华中科技大学同济医学院附属同济医院神经内科,武汉430030;
    4. 中南大学湘雅医院神经内科,长沙410008
  • 出版日期:2015-08-20 发布日期:2015-08-20
  • 通讯作者: 刘静宇,教授,博士生导师,研究方向:医学分子遗传学。 E-mail:Liujy@hust.edu.cn
  • 作者简介:王程,博士后,专业方向:医学分子遗传学。E-mail: gloria1987@126.com
  • 基金资助:
    国家自然科学基金项目(编号:31230045,81271252)和十二五国家科技支撑计划项目(编号:2012BAI09B04)资助

Molecular mechanism of idiopathic basal ganglia calcification

Cheng Wang1, Xuan Xu1,Lulu Li1, Tao Wang2, Min Zhang3,Lu Shen4, Beisha Tang4,Jingyu Liu1   

  1. 1. Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China;
    2. Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China;
    3. Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;
    4. Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China
  • Online:2015-08-20 Published:2015-08-20

摘要: 特发性基底节钙化(Idiopathic basal ganglia calcification, IBGC)俗称Fahr病,是一种以基底节及大脑其他部位钙化为特征的神经系统遗传疾病,患者可出现运动障碍及认知、精神异常,目前尚无有效治疗药物。该病具有遗传异质性,自2012年本课题组发现第一个致病基因SLC20A2以来,现今又发现4个该病的致病基因:PDGFRB,PDGFB,ISG15和XPR1,初步将IBGC的发生机制分别与大脑局部无机磷稳态失衡、血脑屏障功能障碍及IFN-α/β免疫信号过度放大联系起来。文章综述了IBGC的遗传学研究进展,初步探讨了不同基因导致IBGC的分子机理。

关键词: 特发性基底节钙化, SLC20A2, PDGFRB, PDGFB, ISG15, XPR1

Abstract: Idiopathic basal ganglia calcification (IBGC), also known as Fahr’s disease, is an inheritable neurodegenerative syn-drome characterized by mineral deposits in the basal ganglia and other brain regions. Patients with IBGC are often accompa-nied with movement disorders, cognitive impairment as well as psychiatric abnormalities. So far, no therapeutic drug has been developed for the treatment of IBGC. Recently, genetic studies have identified several genes associated with IBGC, including SLC20A2, PDGFRB, PDGFB, ISG15 and XPR1. Loss-of-function mutations in these genes have been associated with dis-turbance in phosphate homeostasis in brain regions, the dysfunction of blood-brain barrier as well as enhanced IFN-?/??immunity. In this review, we summarize the latest research progress in the studies on molecular genetics of IBGC, and discuss the molecular mechanisms underlying the pathophysiology of mutations of different genes.

Key words: IBGC, SLC20A2, PDGFRB, PDGFB, ISG15, XPR1