CSF1R基因突变致ALSP发病研究进展  

Research progress on ALSP caused by CSF1R gene mutations

作　　者：黄正平 江佳薇 刘淑芬 叶小芳 李弥弥 庄建龙 叶励超[1,2] 陈春暖[1,2] HUANG Zhengping;JIANG Jiawei;LIU Shufen;YE Xiaofang;LI Mimi;ZHUANG Jianlong;YE Lichao;CHEN Chunnuan(Department of Neurology,the Second Affiliated Hospital of Fujian Medical University,The Second Clinical Medical College of Fujian Medical University,Quanzhou 362000,China)

机构地区：[1]福建医科大学附属第二医院神经内科,泉州362000 [2]福建医科大学第二临床医学院 [3]福建省泉州市妇幼保健院、儿童医院产前诊断中心

出　　处：《中国神经精神疾病杂志》2024年第3期173-178,共6页Chinese Journal of Nervous and Mental Diseases

基　　金：福建省自然科学基金项目(编号:2023J01104,2023Y9255);泉州科学技术局项目(编号:2023C005YR,2022C025R)。

摘　　要：成人发病的白质脑病合并轴索球样变和色素性胶质细胞(adult-onset leukoencephalopathy with axonal spheroids and pigmented glia,ALSP)是临床罕见的常染色体显性遗传病,其具体的发病机制目前还未明确。集落刺激因子1受体(colony-stimulating factor 1 receptor,CSF1R)是一种细胞表面跨膜酪氨酸激酶受体,与其相关的编码基因突变已被证实是ALSP的潜在致病因素。然而,目前关于CSF1R基因突变致使ALSP发病的具体机制尚不清楚。本文回顾CSF1R基因在ALSP发病过程中的突变位点及致病机制研究,发现CSF1R突变可以通过显性负性效应、功能丧失、单倍体剂量不足及功能获得等机制导致小胶质细胞功能异常,进而引起ALSP的发病。对ALSP病因的深入认识有助于更好地探索潜在的治疗方法。Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia(ALSP) is a clinically rare autosomal dominant genetic disease, and its specific pathogenesis is not yet clear. The colony-stimulating factor 1 receptor(CSF1R) is a transmembrane tyrosine kinase receptor on the cell surface and mutations in the gene encoding it have been identified as potential pathogenic factors for ALSP. However, the specific mechanisms by which CSF1R gene mutations lead to the onset of ALSP are still unclear. After reviewing the mutation sites and pathogenic mechanisms of CSF1R in the pathogenesis of ALSP, CSF1R mutations have been shown to cause microglial dysfunction through mechanisms such as dominant-negative effects, loss of function, haploinsufficiency, and gain of function, thereby leading to the onset of ALSP.A deeper understanding of the causes of ALSP will help in exploring potential treatment methods.

关 键 词：成人发病的白质脑病合并轴索球样变和色素性胶质细胞 脑白质病变 集落刺激因子1受体 遗传性疾病 小胶质细胞 突变 

分 类 号：R742[医药卫生—神经病学与精神病学]