PT - JOURNAL ARTICLE AU - Sen Zhao AU - Yuanqiang Zhang AU - Weisheng Chen AU - Weiyu Li AU - Shengru Wang AU - Lianlei Wang AU - Yanxue Zhao AU - Mao Lin AU - Yongyu Ye AU - Jiachen Lin AU - Yu Zheng AU - Jiaqi Liu AU - Hengqiang Zhao AU - Zihui Yan AU - Yongxin Yang AU - Yingzhao Huang AU - Guanfeng Lin AU - Zefu Chen AU - Zhen Zhang AU - Sen Liu AU - Lichao Jin AU - Zhaoyang Wang AU - Jingdan Chen AU - Yuchen Niu AU - Xiaoxin Li AU - Yong Wu AU - Yipeng Wang AU - Renqian Du AU - Na Gao AU - Hong Zhao AU - Ying Yang AU - Ying Liu AU - Ye Tian AU - Wenli Li AU - Yu Zhao AU - Jia Liu AU - Bin Yu AU - Na Zhang AU - Keyi Yu AU - Xu Yang AU - Shugang Li AU - Yuan Xu AU - Jianhua Hu AU - Zhe Liu AU - Jianxiong Shen AU - Shuyang Zhang AU - Jianzhong Su AU - Anas M Khanshour AU - Yared H Kidane AU - Brandon Ramo AU - Jonathan J Rios AU - Pengfei Liu AU - V. Reid Sutton AU - Jennifer E Posey AU - Zhihong Wu AU - Guixing Qiu AU - Carol A Wise AU - Feng Zhang AU - James R Lupski AU - Jianguo Zhang AU - Nan Wu TI - Diagnostic yield and clinical impact of exome sequencing in early-onset scoliosis (EOS) AID - 10.1136/jmedgenet-2019-106823 DP - 2021 Jan 01 TA - Journal of Medical Genetics PG - 41--47 VI - 58 IP - 1 4099 - http://jmg.bmj.com/content/58/1/41.short 4100 - http://jmg.bmj.com/content/58/1/41.full SO - J Med Genet2021 Jan 01; 58 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.