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Identification of a novel frameshift mutation of the EXT2 gene in a family with multiple osteochondroma

  • Authors:
    • Peng Xia
    • Haikun Xu
    • Qingyang Shi
    • Dejun Li
  • View Affiliations / Copyright

    Affiliations: Department of Spinal Surgery, Orthopedics Hospital, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China, Department of Cardiology, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China, Center for Prenatal Diagnosis, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
    Copyright: © Xia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 105-110
    |
    Published online on: October 29, 2015
       https://doi.org/10.3892/ol.2015.3844
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Abstract

Multiple osteochondroma (MO), also known as multiple hereditary exostoses, is an autosomal dominant skeletal disorder with characteristic multiple cartilage‑capped tumours (osteochondromas or exostoses) growing outward from the metaphyseal region of the long tubular bones. Mutations in exostosin glycosyltransferase 1 (EXT1) or EXT2 are the most commonly associated mutations with MO and are responsible for 70‑95% of cases. In the present study, a genetic analysis was performed on a large family with MO using polymerase chain reaction and direct DNA sequencing of the entire coding regions of EXT1 and EXT2. Sanger sequencing identified a novel heterozygous frameshift mutation, c.119_120delCT (p.Thr40ArgfsX15), in exon 2 of the EXT2 gene in the proband and all other affected individuals, while this deleterious mutation was not detected in the healthy family members and normal controls. The c.119_120delCT mutation is located in the transmembrane region of the EXT2 protein and results in a truncated EXT2 protein lacking 665 amino acids at the C‑terminus, which includes the critical exostosin and glycosyltransferase family 64 domains. Thus, the present study identified a novel causative frameshift mutation in EXT2 from a large MO family. This study is useful for extending the known mutational spectrum of EXT2, for understanding the genetic basis of MO in the patients studied, and for further application of mutation screening in the genetic counseling and subsequent prenatal diagnosis of this family.
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1 

Krooth RS, MacKlin MT and Hilbish TF: Diaphysial aclasis (multiple exostoses) on Guam. Am J Hum Genet. 13:340–347. 1961.PubMed/NCBI

2 

Hennekam RC: Hereditary multiple exostoses. J Med Genet. 28:262–266. 1991. View Article : Google Scholar : PubMed/NCBI

3 

Schmale GA, Conrad EU III and Raskind WH: The natural history of hereditary multiple exostoses. J Bone Joint Surg Am. 76:986–992. 1994.PubMed/NCBI

4 

Bovée JV: Multiple osteochondromas. Orphanet J Rare Dis. 3:32008. View Article : Google Scholar : PubMed/NCBI

5 

Lüdecke HJ, Ahn J, Lin X, Hill A, Wagner MJ, Schomburg L, Horsthemke B and Wells DE: Genomic organization and promoter structure of the human EXT1 gene. Genomics. 40:351–354. 1997. View Article : Google Scholar : PubMed/NCBI

6 

Clines GA, Ashley JA, Shah S and Lovett M: The structure of the human multiple exostoses 2 gene and characterization of homologs in mouse and Caenorhabditis elegans. Genome Res. 7:359–367. 1997.PubMed/NCBI

7 

Wise CA, Clines GA, Massa H, Trask BJ and Lovett M: Identification and localization of the gene for EXTL, a third member of the multiple exostoses gene family. Genome Res. 7:10–16. 1997. View Article : Google Scholar : PubMed/NCBI

8 

Wuyts W, Van Hul W, Hendrickx J, Speleman F, Wauters J, De Boulle K, Van Roy N, Van Agtmael T, Bossuyt P and Willems PJ: Identification and characterization of a novel member of the EXT gene family, EXTL2. Eur J Hum Genet. 5:382–389. 1997.PubMed/NCBI

9 

Van Hul W, Wuyts W, Hendrickx J, Speleman F, Wauters J, De Boulle K, Van Roy N, Bossuyt P and Willems PJ: Identification of a third EXT-like gene (EXTL3) belonging to the EXT gene family. Genomics. 47:230–237. 1998. View Article : Google Scholar : PubMed/NCBI

10 

Senay C, Lind T, Muguruma K, Tone Y, Kitagawa H, Sugahara K, Lidholt K, Lindahl U and Kusche-Gullberg M: The EXT1/EXT2 tumor suppressors: Catalytic activities and role in heparan sulfate biosynthesis. EMBO Rep. 1:282–286. 2000. View Article : Google Scholar : PubMed/NCBI

11 

Lonie L, Porter DE, Fraser M, Cole T, Wise C, Yates L, Wakeling E, Blair E, Morava E, Monaco AP and Ragoussis J: Determination of the mutation spectrum of the EXT1/EXT2 genes in British Caucasian patients with multiple osteochondromas, and exclusion of six candidate genes in EXT negative cases. Hum Mutat. 27:11602006. View Article : Google Scholar : PubMed/NCBI

12 

Ciavarella M, Coco M, Baorda F, Stanziale P, Chetta M, Bisceglia L, Palumbo P, Bengala M, Raiteri P, Silengo M, et al: 20 novel point mutations and one large deletion in EXT1 and EXT2 genes: Report of diagnostic screening in a large Italian cohort of patients affected by hereditary multiple exostosis. Gene. 515:339–348. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Delgado MA, Martinez-Domenech G, Sarrión P, Urreizti R, Zecchini L, Robledo HH, Segura F, de Kremer RD, Balcells S, Grinberg D and Asteggiano CG: A broad spectrum of genomic changes in latinamerican patients with EXT1/EXT2-CDG. Sci Rep. 4:64072014. View Article : Google Scholar : PubMed/NCBI

14 

Wuyts W and Van Hul W: Molecular basis of multiple exostoses: Mutations in the EXT1 and EXT2 genes. Hum Mutat. 15:220–227. 2000. View Article : Google Scholar : PubMed/NCBI

15 

Lind T, Tufaro F, McCormick C, Lindahl U and Lidholt K: The putative tumor suppressors EXT1 and EXT2 are glycosyltransferases required for the biosynthesis of heparan sulfate. J Biol Chem. 273:26265–26268. 1998. View Article : Google Scholar : PubMed/NCBI

16 

McCormick C, Duncan G, Goutsos KT and Tufaro F: The putative tumor suppressors EXT1 and EXT2 form a stable complex that accumulates in the Golgi apparatus and catalyzes the synthesis of heparan sulfate. Proc Natl Acad Sci USA. 97:668–673. 2000. View Article : Google Scholar : PubMed/NCBI

17 

Esko JD and Lindahl U: Molecular diversity of heparan sulfate. J Clin Invest. 108:169–173. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Zak BM, Crawford BE and Esko JD: Hereditary multiple exostoses and heparan sulfate polymerization. Biochim Biophys Acta. 1573:346–355. 2002. View Article : Google Scholar : PubMed/NCBI

19 

Koziel L, Kunath M, Kelly OG and Vortkamp A: Ext1-dependent heparan sulfate regulates the range of Ihh signaling during endochondral ossification. Dev Cell. 6:801–813. 2004. View Article : Google Scholar : PubMed/NCBI

20 

Jennes I, Pedrini E, Zuntini M, Mordenti M, Balkassmi S, Asteggiano CG, Casey B, Bakker B, Sangiorgi L and Wuyts W: Multiple osteochondromas: Mutation update and description of the multiple osteochondromas mutation database (MOdb). Hum Mutat. 30:1620–1627. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Xu L, Xia J, Jiang H, Zhou J, Li H, Wang D, Pan Q, Long Z, Fan C and Deng HX: Mutation analysis of hereditary multiple exostoses in the Chinese. Hum Genet. 105:45–50. 1999. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Xia P, Xu H, Shi Q and Li D: Identification of a novel frameshift mutation of the EXT2 gene in a family with multiple osteochondroma. Oncol Lett 11: 105-110, 2016.
APA
Xia, P., Xu, H., Shi, Q., & Li, D. (2016). Identification of a novel frameshift mutation of the EXT2 gene in a family with multiple osteochondroma. Oncology Letters, 11, 105-110. https://doi.org/10.3892/ol.2015.3844
MLA
Xia, P., Xu, H., Shi, Q., Li, D."Identification of a novel frameshift mutation of the EXT2 gene in a family with multiple osteochondroma". Oncology Letters 11.1 (2016): 105-110.
Chicago
Xia, P., Xu, H., Shi, Q., Li, D."Identification of a novel frameshift mutation of the EXT2 gene in a family with multiple osteochondroma". Oncology Letters 11, no. 1 (2016): 105-110. https://doi.org/10.3892/ol.2015.3844
Copy and paste a formatted citation
x
Spandidos Publications style
Xia P, Xu H, Shi Q and Li D: Identification of a novel frameshift mutation of the EXT2 gene in a family with multiple osteochondroma. Oncol Lett 11: 105-110, 2016.
APA
Xia, P., Xu, H., Shi, Q., & Li, D. (2016). Identification of a novel frameshift mutation of the EXT2 gene in a family with multiple osteochondroma. Oncology Letters, 11, 105-110. https://doi.org/10.3892/ol.2015.3844
MLA
Xia, P., Xu, H., Shi, Q., Li, D."Identification of a novel frameshift mutation of the EXT2 gene in a family with multiple osteochondroma". Oncology Letters 11.1 (2016): 105-110.
Chicago
Xia, P., Xu, H., Shi, Q., Li, D."Identification of a novel frameshift mutation of the EXT2 gene in a family with multiple osteochondroma". Oncology Letters 11, no. 1 (2016): 105-110. https://doi.org/10.3892/ol.2015.3844
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