Improving genetic diagnosis of Mendelian disease with RNA sequencing:a narrative review

作     者：Zhou Zhou Qing Sang Lei Wang 

作者机构：Institute of PediatricsChildren's Hospital of Fudan Universitythe Shanghai Key Laboratory of Medical Epigeneticsthe Intemational Co-laboratory of Medical Epigenetics and Metabolismthe Ministry of Science and Technologythe Institutes of Biomedical Sciencesand the State Key L aboratory of Genetic EngineeringFudan University Shanghai Center for Women and Children's HealthShanghaiChina 

出 版 物：《Journal of Bio-X Research》 (生物组学研究杂志（英文）)

年 卷 期：2022年第5卷第1期

页      面：1-6页

学科分类：100208[医学-临床检验诊断学] 1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：This work was supported by the National Key Research and Development Program of China (Nos. 2018YFC1003800, 2017YFC1001500, and 2016YFC1000600) the National Natural Science Foundation of China (Nos. 81725006, 81822019, 81771581, 81971450, and 81971382) Shanghai Municipal Science and Technology Major Project (No. 2017SHZDZX01) Project of Shanghai Municipal Science and Technology Commission (No. 19JC1411001) the Natural Science Foundation of Shanghai (No. 19ZR1444500) Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission (No. 18SG03) the Foundation of Shanghai Health and Family Planning Commission (No. 20154Y0162) the Capacity Building Planning Program for Shanghai Women and Children’s Health Service, and the Collaborative Innovation Center Project Construction for Shanghai Women and Children’s Health 

主　　题：aberrant splicing genetic diagnosis Mendelian disease review RNA sequencing 

摘      要：Targeted sequencing and whole exome sequencing are the most common approaches used to detect causative variants in Mendelian diseases;however, using DNA-based sequencing techniques, the current molecular diagnostic yield is at best 50%. In recent years, RNA sequencing has been shown to be able to provide a genetic diagnosis in patients whose conditions were previously unable to be identified by DNA analysis. RNA sequencing can reveal expression outliers, aberrant splicing events, allele-specific expression, and new pathogenic variants, and as such can complement and expand on the traditional genomic methods used to diagnose Mendelian diseases. Therefore, RNA sequencing is expected to become a routine method for genetic diagnosis in the future. This article reviews the applications and challenges of RNA sequencing in the genetic diagnosis of Mendelian diseases.