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Novel GCH-1 Mutation in Chinese Families with Dopa-responsive Dystonia (Segawa Disease)

Received: 27 October 2021     Accepted: 12 November 2021     Published: 19 November 2021
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Abstract

The wide array of clinical manifestations of dopa-responsive dystonia (DRD) or Segawa disease and the prevalence of numerous DRD-associated mutations in guanosine triphosphate cyclohydrolase 1 (GCH1) gene makeDRD diagnosis challenging. Methods: In this study, we assessed the clinical and genetic characteristics of two Chinese families with 3 DRD probands. Clinical assessment of DRD-related symptoms was conducted for all participants. All 6 exons of GCH1 were assessed by genetic analyses for individuals with heteroduplex DNA as compared that of controls. Results: The median DRD-onset age was 24 years and the female to male ratio of DRD patients was 8:1. Six out of eight (75%) patients responded to levodopa therapy. The data indicated that the GCH1 sequence had a novel point mutation resulting in T to C transition at position 80 in exon 1 of the cDNA sequence (c.80T>C), which resulting in an amino acid change (L27P) of GCH1 in the probands and their mother in the first DRD family. Conclusion: A novel GCH1 mutation (c.80T>C) was identified in the DRD patients in the first family. Our findings indicate that both clinical symptom assessment and genetic testing should be employed for improving DRD diagnosis.

Published in Clinical Medicine Research (Volume 10, Issue 6)
DOI 10.11648/j.cmr.20211006.13
Page(s) 186-190
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2021. Published by Science Publishing Group

Keywords

Dopa-responsive Dystonia, Guanosine Triphosphate Cyclohydrolase, GCH1, Chinese

References
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[5] Ichinose H, Ohye T, Matsuda Y, Hori T, Blau N, Burlina A, Rouse B, Matalon R, Fujita K, Nagatsu T. Characterization of mouse and human GTP cyclohydrolase I genes. J Biol Chem 1995; 270: 10062-10071.
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[7] Furukawa Y, Lang AE, Trugman JM, Bird TD, Hunter A, Sadeh M, Tagawa T, St George-Hyslop PH, Guttman M, Morris LW, Hornykiewicz O, Shimadzu M, Kish SJ. Gender-related penetrance and GTP-cyclohydrolase I gene mutations in dopa-responsive dystonia. Neurology 1998; 50: 1015-1020.
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[12] Cao L, Zheng L, Tang WG, Xiao Q, Zhang T, Tang HD. Four Novel Mutations in the GCH1 Gene of Chinese Patients with Dopa-Responsive Dystonia. Mov Disord 2010; 25: 755-783.
[13] Nutan Sharma, Ioanna A. Armata, Trisha J. Mutation in 5’upstream region of GCHI gene causes familial dopa-responsive dystonia. Mov Disord 2011; 26: 2140-2141.
[14] Li-hua Yu, Hua-yong Zhou, Fa-yun Hu. Two novel mutations of the GTP cyclohydrolase I gene and genotype–phenotype correlation in Chinese Dopa-responsive dystonia patients. European Journal of Human Genetics 2012; 12: 239-245.
[15] Segawa M, Nomura Y, Yukishita S, Nishiyama N, Yokochi M. Is phenotypic variation of hereditary progressive dystonia with marked diurnal fluctuation/dopa-responsive dystonia (HPD/DRD) caused by the difference of the locus of mutation on the GTP cyclohydrolase 1 (GCH-1) gene? Adv Neurol 2004; 94: 217-223.
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Cite This Article
  • APA Style

    Yang Yang, Lifeng Chen, Lei Wu, Jiarui Yao, Na Wang, et al. (2021). Novel GCH-1 Mutation in Chinese Families with Dopa-responsive Dystonia (Segawa Disease). Clinical Medicine Research, 10(6), 186-190. https://doi.org/10.11648/j.cmr.20211006.13

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    ACS Style

    Yang Yang; Lifeng Chen; Lei Wu; Jiarui Yao; Na Wang, et al. Novel GCH-1 Mutation in Chinese Families with Dopa-responsive Dystonia (Segawa Disease). Clin. Med. Res. 2021, 10(6), 186-190. doi: 10.11648/j.cmr.20211006.13

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    AMA Style

    Yang Yang, Lifeng Chen, Lei Wu, Jiarui Yao, Na Wang, et al. Novel GCH-1 Mutation in Chinese Families with Dopa-responsive Dystonia (Segawa Disease). Clin Med Res. 2021;10(6):186-190. doi: 10.11648/j.cmr.20211006.13

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  • @article{10.11648/j.cmr.20211006.13,
      author = {Yang Yang and Lifeng Chen and Lei Wu and Jiarui Yao and Na Wang and Xiaoqing Su and Dongmei Li and Lina Han and Weiping Wu and Dehui Huang and Tianyu Jiang and Zhenfu Wang},
      title = {Novel GCH-1 Mutation in Chinese Families with Dopa-responsive Dystonia (Segawa Disease)},
      journal = {Clinical Medicine Research},
      volume = {10},
      number = {6},
      pages = {186-190},
      doi = {10.11648/j.cmr.20211006.13},
      url = {https://doi.org/10.11648/j.cmr.20211006.13},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cmr.20211006.13},
      abstract = {The wide array of clinical manifestations of dopa-responsive dystonia (DRD) or Segawa disease and the prevalence of numerous DRD-associated mutations in guanosine triphosphate cyclohydrolase 1 (GCH1) gene makeDRD diagnosis challenging. Methods: In this study, we assessed the clinical and genetic characteristics of two Chinese families with 3 DRD probands. Clinical assessment of DRD-related symptoms was conducted for all participants. All 6 exons of GCH1 were assessed by genetic analyses for individuals with heteroduplex DNA as compared that of controls. Results: The median DRD-onset age was 24 years and the female to male ratio of DRD patients was 8:1. Six out of eight (75%) patients responded to levodopa therapy. The data indicated that the GCH1 sequence had a novel point mutation resulting in T to C transition at position 80 in exon 1 of the cDNA sequence (c.80T>C), which resulting in an amino acid change (L27P) of GCH1 in the probands and their mother in the first DRD family. Conclusion: A novel GCH1 mutation (c.80T>C) was identified in the DRD patients in the first family. Our findings indicate that both clinical symptom assessment and genetic testing should be employed for improving DRD diagnosis.},
     year = {2021}
    }
    

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  • TY  - JOUR
    T1  - Novel GCH-1 Mutation in Chinese Families with Dopa-responsive Dystonia (Segawa Disease)
    AU  - Yang Yang
    AU  - Lifeng Chen
    AU  - Lei Wu
    AU  - Jiarui Yao
    AU  - Na Wang
    AU  - Xiaoqing Su
    AU  - Dongmei Li
    AU  - Lina Han
    AU  - Weiping Wu
    AU  - Dehui Huang
    AU  - Tianyu Jiang
    AU  - Zhenfu Wang
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    PY  - 2021
    N1  - https://doi.org/10.11648/j.cmr.20211006.13
    DO  - 10.11648/j.cmr.20211006.13
    T2  - Clinical Medicine Research
    JF  - Clinical Medicine Research
    JO  - Clinical Medicine Research
    SP  - 186
    EP  - 190
    PB  - Science Publishing Group
    SN  - 2326-9057
    UR  - https://doi.org/10.11648/j.cmr.20211006.13
    AB  - The wide array of clinical manifestations of dopa-responsive dystonia (DRD) or Segawa disease and the prevalence of numerous DRD-associated mutations in guanosine triphosphate cyclohydrolase 1 (GCH1) gene makeDRD diagnosis challenging. Methods: In this study, we assessed the clinical and genetic characteristics of two Chinese families with 3 DRD probands. Clinical assessment of DRD-related symptoms was conducted for all participants. All 6 exons of GCH1 were assessed by genetic analyses for individuals with heteroduplex DNA as compared that of controls. Results: The median DRD-onset age was 24 years and the female to male ratio of DRD patients was 8:1. Six out of eight (75%) patients responded to levodopa therapy. The data indicated that the GCH1 sequence had a novel point mutation resulting in T to C transition at position 80 in exon 1 of the cDNA sequence (c.80T>C), which resulting in an amino acid change (L27P) of GCH1 in the probands and their mother in the first DRD family. Conclusion: A novel GCH1 mutation (c.80T>C) was identified in the DRD patients in the first family. Our findings indicate that both clinical symptom assessment and genetic testing should be employed for improving DRD diagnosis.
    VL  - 10
    IS  - 6
    ER  - 

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Author Information
  • Department of Neurology, the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China

  • Department of Neurosurgery, the First Medical Center, Chinese PLA General Hospital, Beijing, China

  • Department of Neurosurgery, the First Medical Center, Chinese PLA General Hospital, Beijing, China

  • Department of Neurology, the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China

  • Department of Rehabilitation Medicine, the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China

  • Department of Neurology, the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China

  • Department of Neurology, the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China

  • Department of Neurology, the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China

  • Department of Neurology, the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China

  • Department of Neurosurgery, the First Medical Center, Chinese PLA General Hospital, Beijing, China

  • Department of Rehabilitation Medicine, the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China

  • Department of Neurology, the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China

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