Genome sequencing demonstrates high diagnostic yield in children with undiagnosed global developmental delay/intellectual disability: A prospective study
Genome sequencing (GS) has been used in the diagnosis of global developmental delay (GDD)/intellectual disability (ID). However, the performance of GS in patients with inconclusive results from chromosomal microarray analysis (CMA) and exome sequencing (ES) is unknown. We recruited 100 pediatric GDD/ID patients from multiple sites in China from February 2018 to August 2020 for GS. Patients have received at least one genomic diagnostic test before enrollment. Reanalysis of their CMA/ES data was performed. The yield of GS was calculated and explanations for missed diagnoses by CMA/ES were investigated. Clinical utility was assessed by interviewing the parents by phone. The overall diagnostic yield of GS was 21%. Seven cases could have been solved with reanalysis of ES data. Thirteen families were missed by previous CMA/ES due to improper methodology. Two remained unsolved after ES reanalysis due to complex variants missed by ES, and a CNV in untranslated regions. Follow-up of the diagnosed families revealed that nine families experienced changes in clinical management, including identification of targeted treatments, cessation of unnecessary treatment, and considerations for family planning. GS demonstrated high diagnostic yield and clinical utility in this undiagnosed GDD/ID cohort, detecting a wide range of variant types of different sizes in a single workflow.
基金：
Precision Medical Research of National Key Research and Development Program [2018YFC1002200, 2019YFC1005100, 2018YFC1002400]; National Natural Science Foundation of China [81873724, 82070914, 81873671]; Shanghai Shen Kang Hospital Development Center [SHDC12017109]; Shanghai Science and Technology Commission [19140904500]; Jiaotong University Cross Biomedical Engineering [YG2017MS72]; Foundation of Shanghai Municipal Health Commission [shslczdzk05702]; Municipal Education Commission-Gaofeng Clinical Medicine Grant Support [20191908]
第一作者单位：[1]Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Dept Pediat Endocrinol & Genet Metab, Shanghai, Peoples R China[2]Shanghai Inst Pediat Res, Dept Mol Genet, Shanghai, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Dept Pediat Endocrinol & Genet Metab, Shanghai, Peoples R China[2]Shanghai Inst Pediat Res, Dept Mol Genet, Shanghai, Peoples R China[5]Cent South Univ, Ctr Med Genet, Sch Life Sci, Changsha 410078, Peoples R China[6]Cent South Univ, Hunan Key Lab Med Genet, Sch Life Sci, Changsha 410078, Peoples R China[14]Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Dept Clin Genet, Shanghai 200092, Peoples R China[*1]Department of Clinical Genetics, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, 200092 Shanghai, China.[*2]Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, 410078 Changsha, China[*3]Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, 200092 Shanghai, China
推荐引用方式(GB/T 7714)：
Sun Yu,Peng Jing,Liang Desheng,et al.Genome sequencing demonstrates high diagnostic yield in children with undiagnosed global developmental delay/intellectual disability: A prospective study[J].HUMAN MUTATION.2022,43(5):568-581.doi:10.1002/humu.24347.
APA：
Sun, Yu,Peng, Jing,Liang, Desheng,Ye, Xiantao,Xu, Na...&Yu, Yongguo.(2022).Genome sequencing demonstrates high diagnostic yield in children with undiagnosed global developmental delay/intellectual disability: A prospective study.HUMAN MUTATION,43,(5)
MLA：
Sun, Yu,et al."Genome sequencing demonstrates high diagnostic yield in children with undiagnosed global developmental delay/intellectual disability: A prospective study".HUMAN MUTATION 43..5(2022):568-581
