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

Yang Yang; Lifeng Chen; Lei Wu; Jiarui Yao; Na Wang; Xiaoqing Su; Dongmei Li; Lina Han; Weiping Wu; Dehui Huang; Tianyu Jiang; Zhenfu Wang

doi:doi:10.11648/j.cmr.20211006.13

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

Yang Yang, Lifeng Chen, Lei Wu, Jiarui Yao, Na Wang, Xiaoqing Su, Dongmei Li, Lina Han, Weiping Wu, Dehui Huang, Tianyu Jiang, Zhenfu Wang

Published in Clinical Medicine Research (Volume 10, Issue 6)

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), 2024. Published by Science Publishing Group

Keywords

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

References

[1]	Segawa M: Hereditary progressive dystonia with marked diurnal fluctuation. Brain Dev 2011; 33: 195-201.
[2]	McGraw-Hill: Disorders of tetrahydrobiopterin and related biogenic amines. The Metabolic and Molecular Bases of Inherited Diseases 8th ed. New York, NY; 2001: 1725-1776.
[3]	Abeling NG, Duran M, Bakker HD, Stroomer L, Thöny B, Blau N, Booij J, Poll-The BT. Sepiapterin reductase deficiency an autosomal recessive DOPA-responsive dystonia. Mol Genet Metab 2006; 89: 116-120.
[4]	Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG. Clustal W and Clustal X version 2.0. Bioinformatics 2007; 23: 2947-8.
[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.
[6]	Hwu WL, Wang PJ, Hsiao KJ, Wang TR, Chiou YW, Lee YM. Dopa-responsive dystonia induced by a recessive GTP cyclohydrolase I mutation. Hum Genet 1999; 105: 226-230.
[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.
[8]	Bandmann O, Marsden CD, Wood NW: Atypical presentations of dopa-responsive dystonia. Adv Neurol 1998; 78: 283-290.
[9]	Tassin J, Dürr A, Bonnet AM, Gil R, Vidailhet M, Lücking CB, Goas JY, Durif F, Abada M, Echenne B, Motte J, Lagueny A, Lacomblez L, Jedynak P, Bartholomé B, Agid Y, Brice A. Levodopa-responsive dystonia: GTP cyclohydrolaseI or parkin mutations? Brain 2000; 123: 1112-1121.
[10]	Kong CK, Ko CH, Tong SF, Lam CW. Atypical presentation of dopa-responsive dystonia: generalized hypotonia and proximal weakness. Neurology 2001; 57: 1121-1124.
[11]	Chaila EC, McCabe DJ, Delanty N, Costello DJ, Murphy RP. Broadening the Phenotype of Childhood-Onset Dopa-Responsive Dystonia. Arch Neurol 2006; 63: 1185-1188.
[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.
[16]	Tamaru Y, Hirano M, Ito H, Kawamura J, Matsumoto S, Imai T, Ueno S. Clinical similarities of hereditary progressive/dopa responsive dystonia caused by different types of mutations in the GTP cyclohydrolase I gene. J Neurol Neurosurg Psychiatry 1998; 64: 469-473.
[17]	Hirano M, Yanagihara T, Ueno S. Dominant negative effect of GTP cyclohydrolase I mutations in dopa-responsive hereditary progressive dystonia. Ann Neurol 1998; 44: 365-371.

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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
Y1  - 2021/11/19
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

Yang Yang

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

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

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

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

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

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

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

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

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

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

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

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

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Plain Text BibTeX RIS

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

Copy | Download

@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}
}

Copy | Download

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
Y1  - 2021/11/19
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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