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
May-2019 Volume 19 Issue 5

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
May-2019 Volume 19 Issue 5

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

A Chinese pedigree with a novel mutation in GJB1 gene and a rare variation in DHTKD1 gene for diverse Charcot‑Marie‑Tooth diseases

  • Authors:
    • Zhen‑Hua Zhao
    • Zhi‑Ting Chen
    • Rui‑Ling Zhou
    • Yin‑Zhou Wang
  • View Affiliations / Copyright

    Affiliations: Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China, Department of Neurology, Union Hospital, Fujian Medical University, Fuzhou, Fujian 350001, P.R. China
  • Pages: 4484-4490
    |
    Published online on: March 19, 2019
       https://doi.org/10.3892/mmr.2019.10058
  • 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

Charcot‑Marie‑Tooth (CMT) disease is a group of motor and sensory neuropathies with a high degree of pathological and genetic heterogenicity. The present study described 2 patients with CMT in a Chinese Han pedigree. The proband exhibited the classic manifestation of CMT with slowly progressing muscular atrophy and weakness. Electrophysiological examination highlighted axonal and demyelinating features. His mother did not have any symptoms, but did exhibit abnormal electrophysiological results. Next‑generation sequencing technology was employed to screen mutations in the genes associated with inherited motor never diseases. A novel mutation, c.528_530delAGT, in the gap junction protein beta 1 (GJB1) gene for CMTX, and a rare variation, c.2369C>T, in the dehydrogenase E1 and transketolase domain containing 1 (DHTKD1) gene for CMT disease type 2Q (CMT2Q), were identified in the proband and his mother. The results were verified by Sanger sequencing. Although the in silico analysis predicted no change in the 3‑dimensional structure, the clinical and electrophysiological presentation in the pedigree and the high evolutionary conservation of the affected amino acid supported the hypothesis that the c.528_530delAGT mutation in the GJB1 gene may be pathogenic in this pedigree. In silico analysis and high evolutionary conservation suggested the pathogenicity of the c.2369C>T mutation in the DHTKD1 gene; however, the clinical and electrophysiological performances of the proband and his mother did not conform to those of CMT2Q caused by the DHTKD1 gene. The present study provided additional information concerning the range of mutations of the GJB1 gene, which facilitated the understanding of the genotype‑phenotype association of CMT.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Kazamel M and Boes CJ: Charcot marie tooth disease (CMT): Historical perspectives and evolution. J Neurol. 262:801–805. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Timmerman V, Strickland AV and Zuchner S: Genetics of Charcot-Marie-Tooth (CMT) disease within the frame of the human genome project success. Genes (Basel). 5:13–32. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Ionasescu VV, Ionasescu R and Searby C: Screening of dominantly inherited Charcot-Marie-Tooth neuropathies. Muscle Nerve. 16:1232–1238. 1993. View Article : Google Scholar : PubMed/NCBI

4 

Bennett MV, Barrio LC, Bargiello TA, Spray DC, Hertzberg E and Sáez JC: Gap junctions: New tools, new answers, new questions. Neuron. 6:305–320. 1991. View Article : Google Scholar : PubMed/NCBI

5 

Li H and Durbin R: Fast and accurate short read alignment with burrows-wheeler transform. Bioinformatics. 25:1754–1760. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Li R, Li Y, Fang X, Yang H and Wang J, Kristiansen K and Wang J: SNP detection for massively parallel whole-genome resequencing. Genome Res. 19:1124–1132. 2009. View Article : Google Scholar : PubMed/NCBI

7 

McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M and DePristo MA: The genome analysis toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20:1297–1303. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Schwarz JM, Cooper DN, Schuelke M and Seelow D: MutationTaster2: Mutation prediction for the deep-sequencing age. Nat Methods. 11:361–362. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, Heer FT, de Beer TAP, Rempfer C, Bordoli L, et al: SWISS-MODEL: Homology modelling of protein structures and complexes. Nucleic Acids Res. 46:W1. W296–W303. 2018. View Article : Google Scholar : PubMed/NCBI

10 

Bienert S, Waterhouse A, de Beer TA, Tauriello G, Studer G, Bordoli L and Schwede T: The SWISS-MODEL Repository-new features and functionality. Nucleic Acids Res. 45(D1): D313–D319. 2017. View Article : Google Scholar : PubMed/NCBI

11 

Guex N, Peitsch MC and Schwede T: Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer: A historical perspective. Electrophoresis. 30 (Suppl 1):S162–S173. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Benkert P, Biasini M and Schwede T: Toward the estimation of the absolute quality of individual protein structure models. Bioinformatics. 27:343–350. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Bertoni M, Kiefer F, Biasini M, Bordoli L and Schwede T: Modeling protein quaternary structure of homo- and hetero-oligomers beyond binary interactions by homology. Sci Rep. 7:104802017. View Article : Google Scholar : PubMed/NCBI

14 

Shy ME, Blake J, Krajewski K, Fuerst DR, Laura M, Hahn AF, Li J, Lewis RA and Reilly M: Reliability and validity of the CMT neuropathy score as a measure of disability. Neurology. 64:1209–1214. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, et al: Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology. Genet Med. 17:405–424. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Yuan JH, Sakiyama Y, Hashiguchi A, Ando M, Okamoto Y, Yoshimura A, Higuchi Y and Takashima H: Genetic and phenotypic profile of 112 patients with X-linked Charcot-Marie-Tooth disease type 1. Eur J Neurol. 25:1454–1461. 2018. View Article : Google Scholar : PubMed/NCBI

17 

Wang Y and Yin F: A review of X-linked Charcot-Marie-Tooth disease. J Child Neurol. 31:761–772. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Scherer SS, Xu YT, Nelles E, Fischbeck K, Willecke K and Bone LJ: Connexin32-null mice develop demyelinating peripheral neuropathy. Glia. 24:8–20. 1998. View Article : Google Scholar : PubMed/NCBI

19 

Hahn AF, Brown WF, Koopman WJ and Feasby TE: X-linked dominant hereditary motor and sensory neuropathy. Brain. 113:1511–1525. 1990. View Article : Google Scholar : PubMed/NCBI

20 

Williams MM, Tyfield LA, Jardine P, Lunt PW, Stevens DL and Turnpenny PD: HMSN and HNPP. Laboratory service provision in the south west of England-two years' experience. Ann N Y Acad Sci. 883:500–503. 1999. View Article : Google Scholar

21 

Ikegami T, Lin C, Kato M, Itoh A, Nonaka I, Kurimura M, Hirayabashi H, Shinohara Y, Mochizuki A and Hayasaka K: Four novel mutations of the connexin 32 gene in four Japanese families with Charcot-Marie-Tooth disease type 1. Am J Med Genet. 80:352–355. 1998. View Article : Google Scholar : PubMed/NCBI

22 

Deschênes SM, Walcott JL, Wexler TL, Scherer SS and Fischbeck KH: Altered trafficking of mutant connexin32. J Neurosci. 17:9077–9084. 1997. View Article : Google Scholar : PubMed/NCBI

23 

Kleopa KA, Yum SW and Scherer SS: Cellular mechanisms of connexin32 mutations associated with CNS manifestations. J Neurosci Res. 68:522–534. 2002. View Article : Google Scholar : PubMed/NCBI

24 

Yum SW, Kleopa KA, Shumas S and Scherer SS: Diverse trafficking abnormalities of connexin32 mutants causing CMTX. Neurobiol Dis. 11:43–52. 2002. View Article : Google Scholar : PubMed/NCBI

25 

VanSlyke JK, Deschenes SM and Musil LS: Intracellular transport, assembly, and degradation of wild-type and disease-linked mutant gap junction proteins. Mol Biol Cell. 11:1933–1946. 2000. View Article : Google Scholar : PubMed/NCBI

26 

Oh S, Ri Y, Bennett MV, Trexler EB, Verselis VK and Bargiello TA: Changes in permeability caused by connexin 32 mutations underlie X-linked Charcot-Marie-Tooth disease. Neuron. 19:927–938. 1997. View Article : Google Scholar : PubMed/NCBI

27 

Nakagawa S, Maeda S and Tsukihara T: Structural and functional studies of gap junction channels. Curr Opin Struct Biol. 20:423–430. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Nualart-Marti A, Solsona C and Fields RD: Gap junction communication in myelinating glia. Biochim Biophys Acta. 1828:69–78. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Bortolozzi M: What's the function of connexin 32 in the peripheral nervous system? Front Mol Neurosci. 11:2272018. View Article : Google Scholar : PubMed/NCBI

30 

Wang HL, Chang WT, Yeh TH, Wu T, Chen MS and Wu CY: Functional analysis of connexin-32 mutants associated with X-linked dominant Charcot-Marie-Tooth disease. Neurobiol Dis. 15:361–370. 2004. View Article : Google Scholar : PubMed/NCBI

31 

Castro C, Gómez-Hernandez JM, Silander K and Barrio LC: Altered formation of hemichannels and gap junction channels caused by C-terminal connexin-32 mutations. J Neurosci. 19:3752–3760. 1999. View Article : Google Scholar : PubMed/NCBI

32 

Abrams CK, Islam M, Mahmoud R, Kwon T, Bargiello TA and Freidin MM: Functional requirement for a highly conserved charged residue at position 75 in the gap junction protein connexin 32. J Biol Chem. 288:3609–3619. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Shy ME, Siskind C, Swan ER, Krajewski KM, Doherty T, Fuerst DR, Ainsworth PJ, Lewis RA, Scherer SS and Hahn AF: CMT1X phenotypes represent loss of GJB1 gene function. Neurology. 68:849–855. 2007. View Article : Google Scholar : PubMed/NCBI

34 

Panosyan FB, Laura M, Rossor AM, Pisciotta C, Piscosquito G, Burns J, Li J, Yum SW, Lewis RA, Day J, et al: Cross-sectional analysis of a large cohort with X-linked Charcot-Marie-Tooth disease (CMTX1). Neurology. 89:927–935. 2017. View Article : Google Scholar : PubMed/NCBI

35 

Xu WY, Gu MM, Sun LH, Guo WT, Zhu HB, Ma JF, Yuan WT, Kuang Y, Ji BJ, Wu XL, et al: A nonsense mutation in DHTKD1 causes Charcot-Marie-Tooth disease type 2 in a large Chinese pedigree. Am J Hum Genet. 91:1088–1094. 2012. View Article : Google Scholar : PubMed/NCBI

36 

Hagen J, te Brinke H, Wanders RJ, Knegt AC, Oussoren E, Hoogeboom AJ, Ruijter GJ, Becker D, Schwab KO, Franke I, et al: Genetic basis of alpha-aminoadipic and alpha-ketoadipic aciduria. J Inherit Metab Dis. 38:873–879. 2015. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhao ZH, Chen ZT, Zhou RL and Wang YZ: A Chinese pedigree with a novel mutation in GJB1 gene and a rare variation in DHTKD1 gene for diverse Charcot‑Marie‑Tooth diseases. Mol Med Rep 19: 4484-4490, 2019.
APA
Zhao, Z., Chen, Z., Zhou, R., & Wang, Y. (2019). A Chinese pedigree with a novel mutation in GJB1 gene and a rare variation in DHTKD1 gene for diverse Charcot‑Marie‑Tooth diseases. Molecular Medicine Reports, 19, 4484-4490. https://doi.org/10.3892/mmr.2019.10058
MLA
Zhao, Z., Chen, Z., Zhou, R., Wang, Y."A Chinese pedigree with a novel mutation in GJB1 gene and a rare variation in DHTKD1 gene for diverse Charcot‑Marie‑Tooth diseases". Molecular Medicine Reports 19.5 (2019): 4484-4490.
Chicago
Zhao, Z., Chen, Z., Zhou, R., Wang, Y."A Chinese pedigree with a novel mutation in GJB1 gene and a rare variation in DHTKD1 gene for diverse Charcot‑Marie‑Tooth diseases". Molecular Medicine Reports 19, no. 5 (2019): 4484-4490. https://doi.org/10.3892/mmr.2019.10058
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao ZH, Chen ZT, Zhou RL and Wang YZ: A Chinese pedigree with a novel mutation in GJB1 gene and a rare variation in DHTKD1 gene for diverse Charcot‑Marie‑Tooth diseases. Mol Med Rep 19: 4484-4490, 2019.
APA
Zhao, Z., Chen, Z., Zhou, R., & Wang, Y. (2019). A Chinese pedigree with a novel mutation in GJB1 gene and a rare variation in DHTKD1 gene for diverse Charcot‑Marie‑Tooth diseases. Molecular Medicine Reports, 19, 4484-4490. https://doi.org/10.3892/mmr.2019.10058
MLA
Zhao, Z., Chen, Z., Zhou, R., Wang, Y."A Chinese pedigree with a novel mutation in GJB1 gene and a rare variation in DHTKD1 gene for diverse Charcot‑Marie‑Tooth diseases". Molecular Medicine Reports 19.5 (2019): 4484-4490.
Chicago
Zhao, Z., Chen, Z., Zhou, R., Wang, Y."A Chinese pedigree with a novel mutation in GJB1 gene and a rare variation in DHTKD1 gene for diverse Charcot‑Marie‑Tooth diseases". Molecular Medicine Reports 19, no. 5 (2019): 4484-4490. https://doi.org/10.3892/mmr.2019.10058
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