Diagnostic yield and clinical impact of exome sequencing in early-onset scoliosis (EOS).

TitleDiagnostic yield and clinical impact of exome sequencing in early-onset scoliosis (EOS).
Publication TypeJournal Article
Year of Publication2020
AuthorsZhao, S, Zhang, Y, Chen, W, Li, W, Wang, S, Wang, L, Zhao, Y, Lin, M, Ye, Y, Lin, J, Zheng, Y, Liu, J, Zhao, H, Yan, Z, Yang, Y, Huang, Y, Lin, G, Chen, Z, Zhang, Z, Liu, S, Jin, L, Wang, Z, Chen, J, Niu, Y, Li, X, Wu, Y, Wang, Y, Du, R, Gao, N, Zhao, H, Yang, Y, Liu, Y, Tian, Y, Li, W, Zhao, Y, Liu, J, Yu, B, Zhang, N, Yu, K, Yang, X, Li, S, Xu, Y, Hu, J, Liu, Z, Shen, J, Zhang, S, Su, J, Khanshour, AM, Kidane, YH, Ramo, B, Rios, JJ, Liu, P, V Sutton, R, Posey, JE, Wu, Z, Qiu, G, Wise, CA, Zhang, F, Lupski, JR, Zhang, J, Wu, N
Corporate AuthorsDeciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study
JournalJ Med Genet
Date Published2020 May 07
ISSN1468-6244
Abstract

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.

DOI10.1136/jmedgenet-2019-106823
Alternate JournalJ. Med. Genet.
PubMed ID32381727
Grant ListK08 HG008986 / HG / NHGRI NIH HHS / United States
UM1 HG006542 / HG / NHGRI NIH HHS / United States