Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
January-2019 Volume 19 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
January-2019 Volume 19 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

CLCN7 and TCIRG1 mutations in a single family: Evidence for digenic inheritance of osteopetrosis

  • Authors:
    • Yongjia Yang
    • Weihua Ye
    • Jihong Guo
    • Liu Zhao
    • Ming Tu
    • Yu Zheng
    • Liping Li
  • View Affiliations / Copyright

    Affiliations: The Laboratory of Genetics and Metabolism, Hunan Children's Research Institute (HCRI), Hunan Children's Hospital, University of South China, Changsha, Hunan 410007, P.R. China
  • Pages: 595-600
    |
    Published online on: November 13, 2018
       https://doi.org/10.3892/mmr.2018.9648
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Osteopetrosis is a monogenic condition with various inheritance patterns, including autosomal dominant, autosomal recessive and X‑linked. Several disease‑causing genes have been identified and three distinguished types of osteopetrosis have been reported. In the present study, a family with osteopetrosis was investigated. Two novel mutations in chloride voltage‑gated channel 7 (CLCN7) and T cell immune regulator 1 (TCIRG1) were identified by exome sequencing, Sanger sequencing and microsatellite marker analysis. The CLCN7 mutation occurred in amino acid R286, the same position as previously reported. The TCIRG1 mutation occurred on a splicing site of exon 15, thereby leading to a truncated transcript. These two mutations were undetected in 496 ethnic‑matched controls. To the best of our knowledge, this is the first report of human osteopetrosis involving digenic inheritance in a single family, which has important implications for decisions on clinical therapeutic regimen, prognosis evaluation and antenatal diagnosis.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Sobacchi C, Schulz A, Coxon FP, Villa A and Helfrich MH: Osteopetrosis: Genetics, treatment and new insights into osteoclast function. Nat Rev Endocrinol. 9:522–536. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Stark Z and Savarirayan R: Osteopetrosis. Orphanet J Rare Dis. 4:52009. View Article : Google Scholar : PubMed/NCBI

3 

Deng H, He D, Rong P, Xu H, Yuan L, Li L, Lu Q and Guo Y: Novel CLCN7 mutation identified in a Han Chinese family with autosomal dominant osteopetrosis-2. Mol Pain. 12:17448069166526282016. View Article : Google Scholar : PubMed/NCBI

4 

Palagano E, Blair HC, Pangrazio A, Tourkova I, Strina D, Angius A, Cuccuru G, Oppo M, Uva P, Van Hul W, et al: Buried in the middle but guilty: Intronic mutations in the TCIRG1 gene cause human autosomal recessive osteopetrosis. J Bone Miner Res. 30:1814–1821. 2015. View Article : Google Scholar : PubMed/NCBI

5 

Del Fattore A, Cappariello A and Teti A: Genetics, pathogenesis and complications of osteopetrosis. Bone. 42:19–29. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Waguespack SG, Koller DL, White KE, Fishburn T, Carn G, Buckwalter KA, Johnson M, Kocisko M, Evans WE, Foroud T and Econs MJ: Chloride channel 7 (ClCN7) gene mutations and autosomal dominant osteopetrosis, type II. J Bone Miner Res. 18:1513–1518. 2003. View Article : Google Scholar : PubMed/NCBI

7 

Van Wesenbeeck L, Cleiren E, Gram J, Beals RK, Bénichou O, Scopelliti D, Key L, Renton T, Bartels C, Gong Y, et al: Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density. Am J Hum Genet. 272:763–771. 2003. View Article : Google Scholar

8 

Kornak U, Kasper D, Bösl MR, Kaiser E, Schweizer M, Schulz A, Friedrich W, Delling G and Jentsch TJ: Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. Cell. 104:205–215. 2001. View Article : Google Scholar : PubMed/NCBI

9 

Pangrazio A, Pusch M, Caldana E, Frattini A, Lanino E, Tamhankar PM, Phadke S, Lopez AG, Orchard P, Mihci E, et al: Molecular and clinical heterogeneity in CLCN7-dependent osteopetrosis: Report of 20 novel mutations. Hum Mutat. 31:E1071–E1080. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Balemans W, Van Wesenbeeck L and Van Hul W: A clinical and molecular overview of the human osteopetroses. Calcif Tissue Int. 77:263–274. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Del Fattore A, Peruzzi B, Rucci N, Recchia I, Cappariello A, Longo M, Fortunati D, Ballanti P, Iacobini M, Luciani M, et al: Clinical, genetic, and cellular analysis of 49 osteopetrotic patients: Implications for diagnosis and treatment. J Med Genet. 43:315–325. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Cleiren E, Bénichou O, Van Hul E, Gram J, Bollerslev J, Singer FR, Beaverson K, Aledo A, Whyte MP, Yoneyama T, et al: Albers-Schönberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene. Hum Mol Genet. 10:2861–2867. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Lam CW, Tong SF, Wong K, Luo YF, Tang HY, Ha SY and Chan MH: DNA-based diagnosis of malignant osteopetrosis by whole-genome scan using a single-nucleotide polymorphism microarray: Standardization of molecular investigations of genetic diseases due to consanguinity. J Hum Genet. 52:98–101. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Mazzolari E, Forino C, Razza A, Porta F, Villa A and Notarangelo LD: A single-center experience in 20 patients with infantile malignant osteopetrosis. Am J Hematol. 84:473–479. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Li N, Yang Y, Bu J, Zhao C, Lu S, Zhao J, Yan L, Cui L, Zheng R, Li J, et al: An autosomal dominant progressive congenital zonular nuclear cataract linked to chromosome 20p12.2-p11.23. Mol Vis. 12:1506–1510. 2006.PubMed/NCBI

16 

Alam I, Gray AK, Chu K, Ichikawa S, Mohammad KS, Capannolo M, Capulli M, Maurizi A, Muraca M, Teti A, et al: Generation of the first autosomal dominant osteopetrosis type II (ADO2) disease models. Bone. 59:66–75. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Coudert AE, de Vernejoul MC, Muraca M and Del Fattore A: Osteopetrosis and its relevance for the discovery of new functions associated with the skeleton. Int J Endocrinol. 2015:3721562015. View Article : Google Scholar : PubMed/NCBI

18 

Aggarwal S: Skeletal dysplasias with increased bone density: Evolution of molecular pathogenesis in the last century. Gene. 528:41–45. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Wang C, Zhang H, He JW, Gu JM, Hu WW, Hu YQ, Li M, Liu YJ, Fu WZ, Yue H, et al: The virulence gene and clinical phenotypes of osteopetrosis in the Chinese population: Six novel mutations of the CLCN7 gene in twelve osteopetrosis families. J Bone Miner Metab. 30:338–348. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Chu K, Koller DL, Snyder R, Fishburn T, Lai D, Waguespack SG, Foroud T and Econs MJ: Analysis of variation in expression of autosomal dominant osteopetrosis type 2: Searching for modifier genes. Bone. 37:655–661. 2005. View Article : Google Scholar : PubMed/NCBI

21 

Frattini A, Pangrazio A, Susani L, Sobacchi C, Mirolo M, Abinun M, Andolina M, Flanagan A, Horwitz EM, Mihci E, et al: Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis. J Bone Miner Res. 18:1740–1747. 2003. View Article : Google Scholar : PubMed/NCBI

22 

Yu T, Yu Y, Wang J, Yin L, Zhou Y, Ying D, Huang R, Chen H, Wu S, Shen Y, et al: Identification of TCIRG1 and CLCN7 gene mutations in a patient with autosomal recessive osteopetrosis. Mol Med Rep. 9:1191–1196. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yang Y, Ye W, Guo J, Zhao L, Tu M, Zheng Y and Li L: CLCN7 and TCIRG1 mutations in a single family: Evidence for digenic inheritance of osteopetrosis. Mol Med Rep 19: 595-600, 2019.
APA
Yang, Y., Ye, W., Guo, J., Zhao, L., Tu, M., Zheng, Y., & Li, L. (2019). CLCN7 and TCIRG1 mutations in a single family: Evidence for digenic inheritance of osteopetrosis. Molecular Medicine Reports, 19, 595-600. https://doi.org/10.3892/mmr.2018.9648
MLA
Yang, Y., Ye, W., Guo, J., Zhao, L., Tu, M., Zheng, Y., Li, L."CLCN7 and TCIRG1 mutations in a single family: Evidence for digenic inheritance of osteopetrosis". Molecular Medicine Reports 19.1 (2019): 595-600.
Chicago
Yang, Y., Ye, W., Guo, J., Zhao, L., Tu, M., Zheng, Y., Li, L."CLCN7 and TCIRG1 mutations in a single family: Evidence for digenic inheritance of osteopetrosis". Molecular Medicine Reports 19, no. 1 (2019): 595-600. https://doi.org/10.3892/mmr.2018.9648
Copy and paste a formatted citation
x
Spandidos Publications style
Yang Y, Ye W, Guo J, Zhao L, Tu M, Zheng Y and Li L: CLCN7 and TCIRG1 mutations in a single family: Evidence for digenic inheritance of osteopetrosis. Mol Med Rep 19: 595-600, 2019.
APA
Yang, Y., Ye, W., Guo, J., Zhao, L., Tu, M., Zheng, Y., & Li, L. (2019). CLCN7 and TCIRG1 mutations in a single family: Evidence for digenic inheritance of osteopetrosis. Molecular Medicine Reports, 19, 595-600. https://doi.org/10.3892/mmr.2018.9648
MLA
Yang, Y., Ye, W., Guo, J., Zhao, L., Tu, M., Zheng, Y., Li, L."CLCN7 and TCIRG1 mutations in a single family: Evidence for digenic inheritance of osteopetrosis". Molecular Medicine Reports 19.1 (2019): 595-600.
Chicago
Yang, Y., Ye, W., Guo, J., Zhao, L., Tu, M., Zheng, Y., Li, L."CLCN7 and TCIRG1 mutations in a single family: Evidence for digenic inheritance of osteopetrosis". Molecular Medicine Reports 19, no. 1 (2019): 595-600. https://doi.org/10.3892/mmr.2018.9648
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team