Waardenburg综合征的拷贝数变异检测及其致病机制的研究

项目名称： Waardenburg综合征的拷贝数变异检测及其致病机制的研究

项目编号： No.81500803

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 陈红胜

作者单位： 中南大学

项目金额： 17万元

中文摘要： Waardenburg综合征（WS）是最常见的综合征型遗传性耳聋,临床上分4型，已发现6个基因(PAX3、MITF、SOX10、EDN3、EDNRB和SNAI2)与WS的发病有关,目前国内外突变检测主要针对单核苷酸变异，约70%的WS2和15～35%的WS4患者未发现致病基因突变位点。我们前期已收集105例WS患者并进行了致病基因突变筛查，发现17%的WS1和74%的WS2患者病因不明，对其中两个家系的拷贝数变异（CNV）检测发现了2个MITF和SOX10基因的CNV，提示CNV与WS的发病密切相关，但其致病机制还不清楚，国内尚无WS中CNV相关研究的报道。本研究拟在前期工作基础上，采用高通量基因拷贝数检测技术对病因未明的WS患者进行已知致病基因的CNV检测，完善WS致病基因突变谱，并对新发的CNV进行初步的功能实验，探索CNV致WS的发病机制，最终为WS的遗传咨询及产前诊断提供理论依据。

中文关键词： 综合征；常染色体显性遗传；致病基因；基因突变；发病机制

英文摘要： Waardenburg syndrome (WS) is the most common syndromic hereditary deafness,and 6 genes have been found(PAX3,MITF,SOX10, EDN3, EDNRB and SNAI2) associated with the onset of WS.At present, mutations screening mainly for single nucleotide variation,and it shows about 70% of WS2 and 15% to 35% of WS4 have not found the gene mutations.Early we collected 105 patients with WS and carried out disease-causing gene mutation screening for them,but about 17% of WS1 and 74% of WS2 patients,the disease causes of which have been unrevealed.Two copy number variations in MITF and SOX10 have been found in two families, the results of which hint CNV is closely related to the onset of WS, but its pathogenic mechanism is not clear.There is no CNV related domestic report in WS yet. Proposed on the basis of previous work, this study aims to carry out CNV detection using high-throughput gene copy number detection technology and gene function research in the patients with CNV to explore the pathogenesis of WS,which will greatly rich the gene mutations spectrum of WS and eventually provide the theory basis for genetic counseling and prenatal diagnosis for WS families.

英文关键词： Symdrome;Autosomal dominant inheritance;Pathogenic gene;Gene mutation;Pathogenesis