RT Journal Article SR Electronic T1 Diagnostic yield and clinical impact of exome sequencing in early-onset scoliosis (EOS) JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 41 OP 47 DO 10.1136/jmedgenet-2019-106823 VO 58 IS 1 A1 Sen Zhao A1 Yuanqiang Zhang A1 Weisheng Chen A1 Weiyu Li A1 Shengru Wang A1 Lianlei Wang A1 Yanxue Zhao A1 Mao Lin A1 Yongyu Ye A1 Jiachen Lin A1 Yu Zheng A1 Jiaqi Liu A1 Hengqiang Zhao A1 Zihui Yan A1 Yongxin Yang A1 Yingzhao Huang A1 Guanfeng Lin A1 Zefu Chen A1 Zhen Zhang A1 Sen Liu A1 Lichao Jin A1 Zhaoyang Wang A1 Jingdan Chen A1 Yuchen Niu A1 Xiaoxin Li A1 Yong Wu A1 Yipeng Wang A1 Renqian Du A1 Na Gao A1 Hong Zhao A1 Ying Yang A1 Ying Liu A1 Ye Tian A1 Wenli Li A1 Yu Zhao A1 Jia Liu A1 Bin Yu A1 Na Zhang A1 Keyi Yu A1 Xu Yang A1 Shugang Li A1 Yuan Xu A1 Jianhua Hu A1 Zhe Liu A1 Jianxiong Shen A1 Shuyang Zhang A1 Jianzhong Su A1 Anas M Khanshour A1 Yared H Kidane A1 Brandon Ramo A1 Jonathan J Rios A1 Pengfei Liu A1 V. Reid Sutton A1 Jennifer E Posey A1 Zhihong Wu A1 Guixing Qiu A1 Carol A Wise A1 Feng Zhang A1 James R Lupski A1 Jianguo Zhang A1 Nan Wu YR 2021 UL http://jmg.bmj.com/content/58/1/41.abstract AB Background Early-onset scoliosis (EOS), defined by an onset age of scoliosis less than 10 years, conveys significant health risk to affected children. Identification of the molecular aetiology underlying patients with EOS could provide valuable information for both clinical management and prenatal screening.Methods In this study, we consecutively recruited a cohort of 447 Chinese patients with operative EOS. We performed exome sequencing (ES) screening on these individuals and their available family members (totaling 670 subjects). Another cohort of 13 patients with idiopathic early-onset scoliosis (IEOS) from the USA who underwent ES was also recruited.Results After ES data processing and variant interpretation, we detected molecular diagnostic variants in 92 out of 447 (20.6%) Chinese patients with EOS, including 8 patients with molecular confirmation of their clinical diagnosis and 84 patients with molecular diagnoses of previously unrecognised diseases underlying scoliosis. One out of 13 patients with IEOS from the US cohort was molecularly diagnosed. The age at presentation, the number of organ systems involved and the Cobb angle were the three top features predictive of a molecular diagnosis.Conclusion ES enabled the molecular diagnosis/classification of patients with EOS. Specific clinical features/feature pairs are able to indicate the likelihood of gaining a molecular diagnosis through ES.