title: Identification of a novel EXT1 mutation in patients with hereditary multiple exostosis by exome sequencing.
abstract: Hereditary multiple exostosis (HME) is an autosomal inherited skeletal disease whose etiology is not fully understood. To further understand the genetic spectrum of the disease, we analyzed a five-generation Chinese family with HME that have observable inheritance. Exome sequencing was performed on three HME individuals and three unaffected individuals from the family. A downstream study confirmed a new C deletion at codon 442 on exon 5 of the exostosin-1 (EXT1) gene as the only pathogenic site which generated a stop codon and caused the truncation of the protein. We rediscovered the deletion in other affected individuals but not in the unaffected individuals from the family. Upon immunohistochemistry assay, we found that the EXT1 protein level of the patients with the novel mutation in our study was less than the level in the patients without the EXT1 mutation from another unrelated family. For a deeper understanding, we analyzed the mutation spectrum of the EXT1 gene. The present study should facilitate a further understanding of HME.
authors.affiliation: College of Life Science, University of Chinese Academy of Sciences College, Beijing 100049, P.R. China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Liu
authors.affiliation: Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, P.R. China.
authors.forename: Song
authors.initials: S
authors.lastname: Wu
authors.affiliation: Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Duan
authors.affiliation: Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, P.R. China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, P.R. China.
authors.forename: Shiquan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: College of Life Science, University of Chinese Academy of Sciences College, Beijing 100049, P.R. China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Hu
authors.affiliation: BGI Tech Solutions Co., Ltd., Beishan Industrial Zone, Shenzhen 518083, P.R. China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Jia
authors.affiliation: Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, P.R. China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Yang
authors.affiliation: Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, P.R. China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, P.R. China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Li
authors.affiliation: Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, P.R. China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Urology, Zhujiang Hospital of Southern Medical University, Guangzhou 510000, P.R. China.
authors.forename: Youcheng
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, P.R. China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, P.R. China.
authors.forename: Meijian
authors.initials: M
authors.lastname: He
authors.affiliation: Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, P.R. China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: He
authors.affiliation: Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, P.R. China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, P.R. China.
authors.forename: Daping
authors.initials: D
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D002681:China; D059472:Exome; D005097:Exostoses, Multiple Hereditary / Q000235:genetics* / Q000473:pathology; D005260:Female; D016368:Frameshift Mutation; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D017422:Sequence Analysis, DNA / Q000379:methods*; D055815:Young Adult; D000099058:Exostosin 1
chemical_list: D017351:N-Acetylglucosaminyltransferases; D000099058:Exostosin 1