Cellular analysis of a novel mutation p. Ser287Tyr in TOR1A in late-onset isolated dystonia
Background: Variations in TOR1A were thought to be associated with early-onset isolated dystonia. The variant S287Y (NM_000113.2: c.860C > A, p. Ser287Tyr, rs766483672) was found in our late-onset isolated dystonia patient. This missense variant is adjacent to R288Q (c.863G > A, p. Arg288Gln),...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2020-07-01
|
Series: | Neurobiology of Disease |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996120301261 |
id |
doaj-a8e43f5d17ce42afae6d026f34d2c893 |
---|---|
record_format |
Article |
spelling |
doaj-a8e43f5d17ce42afae6d026f34d2c8932021-03-22T08:41:48ZengElsevierNeurobiology of Disease1095-953X2020-07-01140104851Cellular analysis of a novel mutation p. Ser287Tyr in TOR1A in late-onset isolated dystoniaLongjiang Xu0Zhaoqing Yang1Wenwu Li2Zhiling Luo3Changjun Zhang4Xiaoqin Huang5Shaohui Ma6Yuzhou Long7Yan Chu8Yuan Qian9Xiuyun Wang10Hao Sun11The Department of Medical Genetics, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaThe Department of Medical Genetics, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaThe Department of Neurology, The People's Hospital of ChuXiong Yi Autonomous Prefecture, Chuxiong, ChinaThe Department of Ultrasound, Yunnan Fuwai Cardiovascular Hospital, Kunming, ChinaReproductive Medicine Center, Renmin Hospital, Hubei University of Medicine, Shiyan, ChinaThe Department of Medical Genetics, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaThe Department of Medical Genetics, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaThe Second People's Hospital of Yunnan Province, Kunming, ChinaThe Second People's Hospital of Yunnan Province, Kunming, ChinaYunnan Key Laboratory of Laboratory Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, ChinaThe Department of Medical Genetics, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaThe Department of Medical Genetics, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China; Corresponding author at: The Department of Medical Genetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, 935 Jiaoling Road, Kunming, Yunnan 650118, China.Background: Variations in TOR1A were thought to be associated with early-onset isolated dystonia. The variant S287Y (NM_000113.2: c.860C > A, p. Ser287Tyr, rs766483672) was found in our late-onset isolated dystonia patient. This missense variant is adjacent to R288Q (c.863G > A, p. Arg288Gln), which was reported to be associated with isolated dystonia. The potentially pathogenic role of S287Y is not conclusively known. Methods: Cytological and molecular biological analyses were performed in vitro to determine whether this variant damages the structure and function of the cell. Results: Compared with the SH-SY5Y cells overexpressing wild-type TOR1A, the cells overexpressing the protein with S287Y have an enlarged peri-nuclear space. The same changes in nuclear morphology were also found in the cells overexpressing the pathogenic variants ΔE (NM_000113.2:c.904_906delGAG, p. Glu302del), F205I (NM_000113.2:c.613 T > A, p. Phe205Ile), and R288Q (NM_000113.2:c.863G > A, p. Arg288Gln). Mutated proteins with S287Y presented a higher tendency to form dimers under reducing conditions. The same tendencies were observed in other mutated proteins but not in wild-type torsinA. Conclusions: TorsinA with S287Y damages the structure of the cell nucleus and may be a novel pathogenic mutation that causes isolated dystonia.http://www.sciencedirect.com/science/article/pii/S0969996120301261ChineseLate-onset dystoniaTOR1ANovel mutation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Longjiang Xu Zhaoqing Yang Wenwu Li Zhiling Luo Changjun Zhang Xiaoqin Huang Shaohui Ma Yuzhou Long Yan Chu Yuan Qian Xiuyun Wang Hao Sun |
spellingShingle |
Longjiang Xu Zhaoqing Yang Wenwu Li Zhiling Luo Changjun Zhang Xiaoqin Huang Shaohui Ma Yuzhou Long Yan Chu Yuan Qian Xiuyun Wang Hao Sun Cellular analysis of a novel mutation p. Ser287Tyr in TOR1A in late-onset isolated dystonia Neurobiology of Disease Chinese Late-onset dystonia TOR1A Novel mutation |
author_facet |
Longjiang Xu Zhaoqing Yang Wenwu Li Zhiling Luo Changjun Zhang Xiaoqin Huang Shaohui Ma Yuzhou Long Yan Chu Yuan Qian Xiuyun Wang Hao Sun |
author_sort |
Longjiang Xu |
title |
Cellular analysis of a novel mutation p. Ser287Tyr in TOR1A in late-onset isolated dystonia |
title_short |
Cellular analysis of a novel mutation p. Ser287Tyr in TOR1A in late-onset isolated dystonia |
title_full |
Cellular analysis of a novel mutation p. Ser287Tyr in TOR1A in late-onset isolated dystonia |
title_fullStr |
Cellular analysis of a novel mutation p. Ser287Tyr in TOR1A in late-onset isolated dystonia |
title_full_unstemmed |
Cellular analysis of a novel mutation p. Ser287Tyr in TOR1A in late-onset isolated dystonia |
title_sort |
cellular analysis of a novel mutation p. ser287tyr in tor1a in late-onset isolated dystonia |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2020-07-01 |
description |
Background: Variations in TOR1A were thought to be associated with early-onset isolated dystonia. The variant S287Y (NM_000113.2: c.860C > A, p. Ser287Tyr, rs766483672) was found in our late-onset isolated dystonia patient. This missense variant is adjacent to R288Q (c.863G > A, p. Arg288Gln), which was reported to be associated with isolated dystonia. The potentially pathogenic role of S287Y is not conclusively known. Methods: Cytological and molecular biological analyses were performed in vitro to determine whether this variant damages the structure and function of the cell. Results: Compared with the SH-SY5Y cells overexpressing wild-type TOR1A, the cells overexpressing the protein with S287Y have an enlarged peri-nuclear space. The same changes in nuclear morphology were also found in the cells overexpressing the pathogenic variants ΔE (NM_000113.2:c.904_906delGAG, p. Glu302del), F205I (NM_000113.2:c.613 T > A, p. Phe205Ile), and R288Q (NM_000113.2:c.863G > A, p. Arg288Gln). Mutated proteins with S287Y presented a higher tendency to form dimers under reducing conditions. The same tendencies were observed in other mutated proteins but not in wild-type torsinA. Conclusions: TorsinA with S287Y damages the structure of the cell nucleus and may be a novel pathogenic mutation that causes isolated dystonia. |
topic |
Chinese Late-onset dystonia TOR1A Novel mutation |
url |
http://www.sciencedirect.com/science/article/pii/S0969996120301261 |
work_keys_str_mv |
AT longjiangxu cellularanalysisofanovelmutationpser287tyrintor1ainlateonsetisolateddystonia AT zhaoqingyang cellularanalysisofanovelmutationpser287tyrintor1ainlateonsetisolateddystonia AT wenwuli cellularanalysisofanovelmutationpser287tyrintor1ainlateonsetisolateddystonia AT zhilingluo cellularanalysisofanovelmutationpser287tyrintor1ainlateonsetisolateddystonia AT changjunzhang cellularanalysisofanovelmutationpser287tyrintor1ainlateonsetisolateddystonia AT xiaoqinhuang cellularanalysisofanovelmutationpser287tyrintor1ainlateonsetisolateddystonia AT shaohuima cellularanalysisofanovelmutationpser287tyrintor1ainlateonsetisolateddystonia AT yuzhoulong cellularanalysisofanovelmutationpser287tyrintor1ainlateonsetisolateddystonia AT yanchu cellularanalysisofanovelmutationpser287tyrintor1ainlateonsetisolateddystonia AT yuanqian cellularanalysisofanovelmutationpser287tyrintor1ainlateonsetisolateddystonia AT xiuyunwang cellularanalysisofanovelmutationpser287tyrintor1ainlateonsetisolateddystonia AT haosun cellularanalysisofanovelmutationpser287tyrintor1ainlateonsetisolateddystonia |
_version_ |
1724209417164947456 |