C9orf72下游六核苷酸重复区序列变异及其对重复引物PCR解释的影响:一项大型跨国筛选研究

IF 2.5 4区 医学 Q2 CLINICAL NEUROLOGY Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration Pub Date : 2017-04-03 DOI:10.1080/21678421.2016.1262423
Angelica Nordin, C. Akimoto, Anna Wuolikainen, Helena Alstermark, K. Forsberg, P. Baumann, S. Pinto, M. de Carvalho, A. Hübers, Frida Nordin, A. Ludolph, Jochen H Weishaupt, T. Meyer, T. Grehl, K. Schweikert, Markus Weber, Christian Burkhardt, C. Neuwirth, T. Holmøy, M. Morita, O. Tysnes, M. Benatar, J. Wuu, D. Lange, C. Bisgård, N. Asgari, I. Tarvainen, T. Brännström, P. Andersen
{"title":"C9orf72下游六核苷酸重复区序列变异及其对重复引物PCR解释的影响:一项大型跨国筛选研究","authors":"Angelica Nordin, C. Akimoto, Anna Wuolikainen, Helena Alstermark, K. Forsberg, P. Baumann, S. Pinto, M. de Carvalho, A. Hübers, Frida Nordin, A. Ludolph, Jochen H Weishaupt, T. Meyer, T. Grehl, K. Schweikert, Markus Weber, Christian Burkhardt, C. Neuwirth, T. Holmøy, M. Morita, O. Tysnes, M. Benatar, J. Wuu, D. Lange, C. Bisgård, N. Asgari, I. Tarvainen, T. Brännström, P. Andersen","doi":"10.1080/21678421.2016.1262423","DOIUrl":null,"url":null,"abstract":"Abstract A large GGGGCC-repeat expansion mutation (HREM) in C9orf72 is the most common known cause of ALS and FTD in European populations. Sequence variations immediately downstream of the HREM region have previously been observed and have been suggested to be one reason for difficulties in interpreting RP-PCR data. Our objective was to determine the properties of these sequence variations with regard to prevalence, the range of variation, and effect on disease prognosis. We screened a multi-national cohort (n = 6981) for the HREM and samples with deviant RP-PCR curves were identified. The deviant samples were subsequently sequenced to determine sequence alteration. Our results show that in the USA and European cohorts (n = 6508) 10.7% carried the HREM and 3% had a sequence variant, while no HREM or sequence variants were observed in the Japanese cohort (n = 473). Sequence variations were more common on HREM alleles; however, certain population specific variants were associated with a non-expanded allele.In conclusion, we identified 38 different sequence variants, most located within the first 50 bp downstream of the HREM region. Furthermore, the presence of an HREM was found to be coupled to a lower age of onset and a shorter disease survival, while sequence variation did not have any correlation with these parameters.","PeriodicalId":7740,"journal":{"name":"Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2017-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678421.2016.1262423","citationCount":"16","resultStr":"{\"title\":\"Sequence variations in C9orf72 downstream of the hexanucleotide repeat region and its effect on repeat-primed PCR interpretation: a large multinational screening study\",\"authors\":\"Angelica Nordin, C. Akimoto, Anna Wuolikainen, Helena Alstermark, K. Forsberg, P. Baumann, S. Pinto, M. de Carvalho, A. Hübers, Frida Nordin, A. Ludolph, Jochen H Weishaupt, T. Meyer, T. Grehl, K. Schweikert, Markus Weber, Christian Burkhardt, C. Neuwirth, T. Holmøy, M. Morita, O. Tysnes, M. Benatar, J. Wuu, D. Lange, C. Bisgård, N. Asgari, I. Tarvainen, T. Brännström, P. Andersen\",\"doi\":\"10.1080/21678421.2016.1262423\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Abstract A large GGGGCC-repeat expansion mutation (HREM) in C9orf72 is the most common known cause of ALS and FTD in European populations. Sequence variations immediately downstream of the HREM region have previously been observed and have been suggested to be one reason for difficulties in interpreting RP-PCR data. Our objective was to determine the properties of these sequence variations with regard to prevalence, the range of variation, and effect on disease prognosis. We screened a multi-national cohort (n = 6981) for the HREM and samples with deviant RP-PCR curves were identified. The deviant samples were subsequently sequenced to determine sequence alteration. Our results show that in the USA and European cohorts (n = 6508) 10.7% carried the HREM and 3% had a sequence variant, while no HREM or sequence variants were observed in the Japanese cohort (n = 473). Sequence variations were more common on HREM alleles; however, certain population specific variants were associated with a non-expanded allele.In conclusion, we identified 38 different sequence variants, most located within the first 50 bp downstream of the HREM region. Furthermore, the presence of an HREM was found to be coupled to a lower age of onset and a shorter disease survival, while sequence variation did not have any correlation with these parameters.\",\"PeriodicalId\":7740,\"journal\":{\"name\":\"Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2017-04-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1080/21678421.2016.1262423\",\"citationCount\":\"16\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/21678421.2016.1262423\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/21678421.2016.1262423","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 16

摘要

摘要C9orf72中的一个大GGGGCC重复扩增突变(HREM)是欧洲人群中ALS和FTD最常见的已知原因。先前已经观察到HREM区域下游的序列变化,并认为这是解释RP-PCR数据困难的原因之一。我们的目的是确定这些序列变异在患病率、变异范围和对疾病预后的影响方面的特性。我们筛选了一个多国队列(n = 6981),并鉴定出具有偏差RP-PCR曲线的样品。随后对异常样本进行测序,以确定序列变化。我们的结果表明,在美国和欧洲的队列中(n = 6508)10.7%携带HREM,3%有序列变异,而在日本队列中没有观察到HREM或序列变异(n = 473)。HREM等位基因的序列变异更为常见;然而,某些群体特异性变异与非扩增等位基因相关。总之,我们确定了38个不同的序列变体,大多数位于前50个 HREM区域下游的bp。此外,发现HREM的存在与较低的发病年龄和较短的疾病生存期有关,而序列变异与这些参数没有任何相关性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Sequence variations in C9orf72 downstream of the hexanucleotide repeat region and its effect on repeat-primed PCR interpretation: a large multinational screening study
Abstract A large GGGGCC-repeat expansion mutation (HREM) in C9orf72 is the most common known cause of ALS and FTD in European populations. Sequence variations immediately downstream of the HREM region have previously been observed and have been suggested to be one reason for difficulties in interpreting RP-PCR data. Our objective was to determine the properties of these sequence variations with regard to prevalence, the range of variation, and effect on disease prognosis. We screened a multi-national cohort (n = 6981) for the HREM and samples with deviant RP-PCR curves were identified. The deviant samples were subsequently sequenced to determine sequence alteration. Our results show that in the USA and European cohorts (n = 6508) 10.7% carried the HREM and 3% had a sequence variant, while no HREM or sequence variants were observed in the Japanese cohort (n = 473). Sequence variations were more common on HREM alleles; however, certain population specific variants were associated with a non-expanded allele.In conclusion, we identified 38 different sequence variants, most located within the first 50 bp downstream of the HREM region. Furthermore, the presence of an HREM was found to be coupled to a lower age of onset and a shorter disease survival, while sequence variation did not have any correlation with these parameters.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
5.40
自引率
10.70%
发文量
64
期刊介绍: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration is an exciting new initiative. It represents a timely expansion of the journal Amyotrophic Lateral Sclerosis in response to the clinical, imaging pathological and genetic overlap between ALS and frontotemporal dementia. The expanded journal provides outstanding coverage of research in a wide range of issues related to motor neuron diseases, especially ALS (Lou Gehrig’s disease) and cognitive decline associated with frontotemporal degeneration. The journal also covers related disorders of the neuroaxis when relevant to these core conditions.
期刊最新文献
The correlation between social support, coping style, advance care planning readiness, and quality of life in patients with amyotrophic lateral sclerosis: a cross-sectional study. Effects of COVID-19 on motor neuron disease mortality in the United States: a population-based cross-sectional study SOD1 gene screening in ALS – frequency of mutations, patients’ attitudes to genetic information and transition to tofersen treatment in a multi-center program How to break the news in amyotrophic lateral sclerosis/motor neuron disease: practical guidelines from experts A nurse coaching intervention to improve support to individuals living with ALS.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1