神经嵴发育异常导致综合征型耳聋的机制  

Progress in the study of syndromic hearing loss resulted from neural crest abnormalities

作　　者：刘亚兰[1,2,3] 张华[4] 冯永[1,2,3] 

机构地区：[1]中南大学湘雅医院耳鼻咽喉头颈外科,长沙410008 [2]耳鼻咽喉重大疾病研究湖南省重点实验室,长沙410008 [3]中国医学遗传学国家重点实验室,长沙410078 [4]上海交通大学医学院附属仁济医院耳鼻喉科,上海200127

出　　处：《遗传》2014年第11期1131-1144,共14页Hereditas（Beijing)

基　　金：国家自然科学基金项目(编号:81170923;81470705;81260160);湖南省自然科学基金项目(编号:14JJ7009)资助

摘　　要：综合征型耳聋(Syndromic hearing loss,SHL)现已报道400多种,大多数发病率低,临床常见的有Waardenburg综合征(WS)、先天性小耳畸形综合征、前庭导水管扩大综合征等。因SHL具有极强的临床和遗传异质性,所以对其遗传基础及发病机制的研究变得十分困难。以SOX10和PAX3为中心的基因作用网络引起的神经嵴细胞功能异常与WS、小耳畸形及前庭导水管扩大等表型相关。本课题组前期研究也证实该基因网络参与WS的发病机制。文章针对神经嵴发育异常导致相关综合征型耳聋的发病机制的研究进展进行了系统的阐述,分析并归纳了与综合征型耳聋发病相关的神经嵴发育异常基因互作网络,以期为系统地研究常见综合征型耳聋致病基因的定位克隆以及发病机制提供研究思路和理论基础。More than 400 types of syndromic hearing loss （SHL） have been reported so far, in which Waardenburg syndrome （WS）, congenital microtia syndrome （CMS）, and large vestibular aqueduct syndrome （LVAS） are the most common ones in clinic. However, it is difficult to study the genetic basis and pathogenesis of SHL in a system- atical way because of the strong clinical and genetic heterogeneity of SHL. Dysfunction of neural crest cells （NCC）, which are caused by the gene interaction network extended from SOXIO and PAX3, are relevant to the phenotype of WS, CMS and LVAS. Our previous study also confirmed that the gene network was involved in the pathogenesis ofWS. In this review, we summarize research progress in the pathogenic mechanisms of SHL resulted from defects in neural crest decelopment, and provide the gene interaction network of neural crest abnormalities resulting in SHL, and hope to provide research ideas and theoretical basis for the systematical study on pathogenesis of common SHL.

关 键 词：综合征型耳聋 神经嵴 基因突变 基因互作 

分 类 号：R764[医药卫生—耳鼻咽喉科]