Rare coding variants in MAPK7 predispose to adolescent idiopathic scoliosis

Wenjie Gao, Chong Chen, Taifeng Zhou, Shulan Yang, Bo Gao, Hang Zhou, Chengjie Lian, Zizhao Wu, Xianjian Qiu, Xiaoming Yang, Esam Alattar, Wentao Liu, Deying Su, Silong Sun, Yulan Chen, Kenneth M.C. Cheung, Youqiang Song, Keith K.D. Luk, Danny Chan, Pak Chung ShamChao Xing, Chiea Chuen Khor, Gabriel Liu, Junlin Yang, Yubin Deng, Dingjun Hao, Dongsheng Huang, Quan Zhen Li, Caixia Xu, Peiqiang Su

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Adolescent idiopathic scoliosis (AIS) is a complex genetic disorder characterized by three-dimensional spinal curvatures, affecting 2%–3% of school age children, yet the causes underlying AIS are not well understood. Here, we first conducted a whole-exome sequencing and linkage analysis on a three-generation Chinese family with autosomal-dominant (AD) AIS, and then performed targeted sequencing in a discovery cohort comprising 20 AD AIS families and 86 simplex patients, and finally identified three disease-associated missense variants (c.886G> A, c.1943C> T, and c.1760C> T) in the MAPK7 gene (encoding mitogen-activated protein kinase 7). Genotyping of the three rare variants in a Chinese replication cohort comprising 1,038 simplex patients and 1,841 controls showed that their combined allele frequency was significantly over-represented in patients as compared with controls (2.0% [41/2,076] vs. 0.7% [27/3,682]; odds ratio = 2.7; P = 2.8 × 10−5). In vitro, we demonstrated that the three MAPK7 mutants disrupted nuclear translocation in cellular models, which is necessary for the normal function of MAPK7. In vivo, we also conducted CRISPR/Cas9-mediated deletion of mapk7 in zebrafish recapitulating the characteristic phenotype of idiopathic scoliosis. Taken together, our findings suggest that rare coding variants in MAPK7 predispose to AIS, providing clues to understanding the mechanisms of AIS.

Original languageEnglish (US)
Pages (from-to)1500-1510
Number of pages11
JournalHuman mutation
Issue number11
StatePublished - Nov 2017


  • CRISPR/Cas9
  • MAPK7
  • adolescent idiopathic scoliosis
  • whole-exome sequencing
  • zebrafish

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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