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. 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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.
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.