Open Access

Identification of a novel mutation in the EXT1 gene from a patient with multiple osteochondromas by exome sequencing

  • Authors:
    • Guolin Hong
    • Xiaoyan Guo
    • Wei Yan
    • Qianqian Li
    • Hailing Zhao
    • Ping Ma
    • Xiao Hu
  • View Affiliations

  • Published online on: December 29, 2016     https://doi.org/10.3892/mmr.2016.6086
  • Pages: 657-664
  • Copyright: © Hong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Multiple osteochondromas (MO) is an autosomal skeletal disease with an elusive molecular mechanism. To further elucidate the genetic mechanism of the disease a three‑generation Chinese family with MO was observed and researched, and a novel frameshift mutation (c.335_336insA) in the exotosin 1 (EXT1) gene of one patient with MO was observed through exome sequencing. This was further validated by Sanger sequencing and comparison with 200 unrelated healthy controls. Immunohistochemistry and multiple sequence alignment were performed to determine the pathogenicity of the candidate mutation. Multiple sequence alignment suggested that codon 335 and 336 in the EXT1 gene were highly conserved regions in vertebrates. Immunohistochemistry revealed that EXT1 protein expression levels were decreased in a patient with MO and this mutation compared with a patient with MO who had no EXT1 mutation. Owing to the appearance of c.335_336insA in exon 1 of EXT1, a premature stop codon was introduced, resulting in truncated EXT1. As a result integrated and functional EXT1 was reduced. EXT1 is involved in the biosynthesis of heparan sulfate (HS), an essential molecule, and its dysfunction may lead to MO. The novel mutation of c.335_336insA in the EXT1 gene reported in the present study has enlarged the causal mutation spectrum of MO, and may assist genetic counseling and prenatal diagnosis of MO.
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February-2017
Volume 15 Issue 2

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Spandidos Publications style
Hong G, Guo X, Yan W, Li Q, Zhao H, Ma P and Hu X: Identification of a novel mutation in the EXT1 gene from a patient with multiple osteochondromas by exome sequencing. Mol Med Rep 15: 657-664, 2017.
APA
Hong, G., Guo, X., Yan, W., Li, Q., Zhao, H., Ma, P., & Hu, X. (2017). Identification of a novel mutation in the EXT1 gene from a patient with multiple osteochondromas by exome sequencing. Molecular Medicine Reports, 15, 657-664. https://doi.org/10.3892/mmr.2016.6086
MLA
Hong, G., Guo, X., Yan, W., Li, Q., Zhao, H., Ma, P., Hu, X."Identification of a novel mutation in the EXT1 gene from a patient with multiple osteochondromas by exome sequencing". Molecular Medicine Reports 15.2 (2017): 657-664.
Chicago
Hong, G., Guo, X., Yan, W., Li, Q., Zhao, H., Ma, P., Hu, X."Identification of a novel mutation in the EXT1 gene from a patient with multiple osteochondromas by exome sequencing". Molecular Medicine Reports 15, no. 2 (2017): 657-664. https://doi.org/10.3892/mmr.2016.6086