通过全外显子组测序诊断两例由TCTN1基因新突变导致的Joubert综合征  

Diagnosis of two cases from one family with Joubert syndrome caused by novel mutations of TCTN1 gene by whole exome sequencing

作　　者：王环环[1] 蒋雯婷[1] 戴梦瑶[1] 肖冰[1] 徐燕[1] 孙昱[1] 刘宇[1] 应晓敏 孙云龙 魏巍 季星[1] Wang Huanhuan;Jiang Wenting;Dai Mengyao;Xiao Bing;Xu Yan;Sun Yu;Liu Yu;Ying Xiaomin;Sun Yunlong;Wei Wei;Ji Xing(Shanghai Institute for Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China)

机构地区：[1]上海交通大学医学院附属新华医院上海市儿科医学研究所,200092

出　　处：《中华医学遗传学杂志》2019年第7期686-689,共4页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(81601293);上海市卫计委科研项目(20174Y0210).

摘　　要：目的明确一家系中两例临床表现为Joubert综合征的异常胎儿的遗传学病因。方法应用全外显子组测序技术分析两例胎儿的DNA,用Sanger测序对胎儿及其父母进行突变位点的验证,并通过cDNA分析两个突变位点的致病机制。结果测序显示两例胎儿均携带TCTN1的两个新突变,分别位于第2内含子的c.342-8A>G和第12内含子的c.1494+1G>A。cDNA分析显示两个突变均影响mRNA的正常剪接,从而导致产生截短的蛋白。结论明确TCTN1基因的两个新突变为该家系的发病原因,上述新突变的发现进一步丰富了TCTN1的突变谱。Objective To explore the pathogenesis of two fetuses from one family affected with Joubert syndrome (JS). Methods Whole exome sequencing was employed to screen potential mutations in both fetuses. Suspected mutations were verified by Sanger sequencing. Impact of intronic mutations on DNA transcription was validated by cDNA analysis. Results Two novel TCTN1 mutations, c. 342-8A>G and c. 1494+ 1G>A, were identified in exons 2 and 12, respectively.cDNA analysis confirmed the pathogenic nature of both mutations with interference of normal splicing resulting in production of truncated proteins. Conclusion The genetic etiology of the family affected with JS has been identified.Above findings have enriched the mutation spectrum of TCTN1gene and facilitated understanding of the genotype-phenotype correlation of JS.

关 键 词：JOUBERT综合征 TCTN1基因 全外显子测序 新突变 

分 类 号：R4[医药卫生—临床医学] R714