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Study of the collagen type VI alpha 3 (COL6A3) gene in Parkinson’s disease

BACKGROUND: To date, the genetic contribution to Parkinson’s disease (PD) remains unclear. Mutations in the collagen type VI alpha 3 (COL6A3) gene were recently identified as a cause of isolated dystonia. Since PD and dystonia are closely related disorders with shared clinical and genetic characteri...

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Autores principales: Jin, Chong-Yao, Zheng, Ran, Lin, Zhi-Hao, Xue, Nai-Jia, Chen, Ying, Gao, Ting, Yan, Yi-Qun, Fang, Yi, Yan, Ya-Ping, Yin, Xin-Zhen, Tian, Jun, Pu, Jia-Li, Zhang, Bao-Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106155/
https://www.ncbi.nlm.nih.gov/pubmed/33964895
http://dx.doi.org/10.1186/s12883-021-02215-7
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author Jin, Chong-Yao
Zheng, Ran
Lin, Zhi-Hao
Xue, Nai-Jia
Chen, Ying
Gao, Ting
Yan, Yi-Qun
Fang, Yi
Yan, Ya-Ping
Yin, Xin-Zhen
Tian, Jun
Pu, Jia-Li
Zhang, Bao-Rong
author_facet Jin, Chong-Yao
Zheng, Ran
Lin, Zhi-Hao
Xue, Nai-Jia
Chen, Ying
Gao, Ting
Yan, Yi-Qun
Fang, Yi
Yan, Ya-Ping
Yin, Xin-Zhen
Tian, Jun
Pu, Jia-Li
Zhang, Bao-Rong
author_sort Jin, Chong-Yao
collection PubMed
description BACKGROUND: To date, the genetic contribution to Parkinson’s disease (PD) remains unclear. Mutations in the collagen type VI alpha 3 (COL6A3) gene were recently identified as a cause of isolated dystonia. Since PD and dystonia are closely related disorders with shared clinical and genetic characteristics, we explored the association between COL6A3 and PD in a Chinese cohort. METHODS: We performed genetic screening of COL6A3 in a Chinese cohort of 173 patients with sporadic PD and 200 healthy controls. We identified variants that are likely to have pathogenic effects based on: 1) a minor allele frequency of < 0.01; and 2) the variant being recognized as deleterious by at least 15 different in silico predicting tools. Finally, we tested the aggregate burden of COL6A3 on PD via SKAT-O analysis. RESULTS: First, we found compound heterozygous COL6A3 gene mutations in one early-onset PD patients. Then, we explored whether COL6A3 variants contributed to increased risk of developing PD in a Chinese population. We detected 21 rare non-synonymous variants. Pathogenicity predictions identified 7 novel non-synonymous variants as likely to be pathogenic. SKAT-O analysis further revealed that an aggregate burden of variants in COL6A3 contributes to PD (p = 0.038). CONCLUSION: An increased aggregate burden of the COL6A3 gene was detected in patients with PD.
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spelling pubmed-81061552021-05-10 Study of the collagen type VI alpha 3 (COL6A3) gene in Parkinson’s disease Jin, Chong-Yao Zheng, Ran Lin, Zhi-Hao Xue, Nai-Jia Chen, Ying Gao, Ting Yan, Yi-Qun Fang, Yi Yan, Ya-Ping Yin, Xin-Zhen Tian, Jun Pu, Jia-Li Zhang, Bao-Rong BMC Neurol Research BACKGROUND: To date, the genetic contribution to Parkinson’s disease (PD) remains unclear. Mutations in the collagen type VI alpha 3 (COL6A3) gene were recently identified as a cause of isolated dystonia. Since PD and dystonia are closely related disorders with shared clinical and genetic characteristics, we explored the association between COL6A3 and PD in a Chinese cohort. METHODS: We performed genetic screening of COL6A3 in a Chinese cohort of 173 patients with sporadic PD and 200 healthy controls. We identified variants that are likely to have pathogenic effects based on: 1) a minor allele frequency of < 0.01; and 2) the variant being recognized as deleterious by at least 15 different in silico predicting tools. Finally, we tested the aggregate burden of COL6A3 on PD via SKAT-O analysis. RESULTS: First, we found compound heterozygous COL6A3 gene mutations in one early-onset PD patients. Then, we explored whether COL6A3 variants contributed to increased risk of developing PD in a Chinese population. We detected 21 rare non-synonymous variants. Pathogenicity predictions identified 7 novel non-synonymous variants as likely to be pathogenic. SKAT-O analysis further revealed that an aggregate burden of variants in COL6A3 contributes to PD (p = 0.038). CONCLUSION: An increased aggregate burden of the COL6A3 gene was detected in patients with PD. BioMed Central 2021-05-08 /pmc/articles/PMC8106155/ /pubmed/33964895 http://dx.doi.org/10.1186/s12883-021-02215-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Jin, Chong-Yao
Zheng, Ran
Lin, Zhi-Hao
Xue, Nai-Jia
Chen, Ying
Gao, Ting
Yan, Yi-Qun
Fang, Yi
Yan, Ya-Ping
Yin, Xin-Zhen
Tian, Jun
Pu, Jia-Li
Zhang, Bao-Rong
Study of the collagen type VI alpha 3 (COL6A3) gene in Parkinson’s disease
title Study of the collagen type VI alpha 3 (COL6A3) gene in Parkinson’s disease
title_full Study of the collagen type VI alpha 3 (COL6A3) gene in Parkinson’s disease
title_fullStr Study of the collagen type VI alpha 3 (COL6A3) gene in Parkinson’s disease
title_full_unstemmed Study of the collagen type VI alpha 3 (COL6A3) gene in Parkinson’s disease
title_short Study of the collagen type VI alpha 3 (COL6A3) gene in Parkinson’s disease
title_sort study of the collagen type vi alpha 3 (col6a3) gene in parkinson’s disease
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106155/
https://www.ncbi.nlm.nih.gov/pubmed/33964895
http://dx.doi.org/10.1186/s12883-021-02215-7
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