先天性颅神经异常支配性疾病的致病基因及其分子机制研究进展  

Research progress on pathogenic gene and molecular mechanism of congenital cranial dysinnervation disorders

作　　者：赵安迪(综述) 刘虎(审校)[1] Zhao Andi;Liu Hu(Department of Ophthalmology,The First Affiliated Hospital with Nanjing Medical University,Nanjing 210029,China)

机构地区：[1]南京医科大学第一附属医院眼科,南京210029

出　　处：《中华实验眼科杂志》2024年第10期938-944,共7页Chinese Journal Of Experimental Ophthalmology

基　　金：国家自然科学基金面上项目(82273159)。

摘　　要：先天性颅神经异常支配性疾病(CCDDs)是由于特定的颅神经核/颅神经发育异常或缺如,轴突生长导向异常,从而引起原发或继发肌肉异常支配的一组先天性眼球运动障碍。CCDDs呈散发或家族性遗传,目前已报道了数个致病基因,包括先天性眼外肌纤维化的致病基因KIF 21A、TUBB3、TUBB2B、PHOX2 A,引起Duane眼球后退综合征的致病基因CHN 1、MAFB、SALL4、HOXA1,引起水平注视麻痹伴进行性脊柱侧弯的基因ROBO 3等。本文基于编码蛋白的亚细胞定位及功能将这些基因分为以下3类:参与微管的生长及组装(KIF 21A、TUBB3、TUBB2 B)、调控基因转录(PHOX 2A/ARIX、MAFB、SALL4、HOXA1、HOXB1)和影响信号转导(CHN 1、ROBO3)。本文就CCDDs的分子遗传学及致病机制研究进展进行综述。Congenital cranial dysinnervation disorders(CCDDs)refer to a collection of congenital ocular motility disorders resulting from defects or abnormalities in the development of specific cranial nerves/nuclei with axonal guidance that cause primary or secondary dysinnervation.CCDDs may be familial or sporadic.Currently,multiple genes have been identified as pathogenic.For example,variants of KIF 21A,TUBB3,TUBB2 B and PHOX 2 A may cause congenital fibrosis of extraocular muscle,variants of CHN 1,MAFB,SALL4 and HOXA 1 may cause Duane retraction syndrome,and variants of ROBO 3 may cause horizontal gaze palsy with progressive scoliosis.Based on the reported subcellular locations and functional classifications of these coded proteins,pathogenic genes have been grouped into three categories:promoting microtubule growth and assembly(KIF 21A,TUBB3,TUBB2 B),regulating gene transcription(PHOX 2A/ARIX,MAFB,SALL4,HOXA1,HOXB1),and affecting signal transduction(CHN 1,ROBO3).This article reviews recent insights into the genetics and molecular mechanisms of CCDDs.

关 键 词：先天性颅神经异常支配性疾病 转录因子 信号转导 微管 轴突导向 

分 类 号：R741[医药卫生—神经病学与精神病学] R771.3[医药卫生—临床医学]