A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD.
A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD.
复制标题
DOI：
10.1016/j.neuron.2011.09.010
复制
发表时间：
2011-10-20
期刊：
影响因子：
16.2
通讯作者：
Traynor BJ
中科院分区：
文献类型：
--
作者：
Renton AE;Majounie E;Waite A;Simón-Sánchez J;Rollinson S;Gibbs JR;Schymick JC;Laaksovirta H;van Swieten JC;Myllykangas L;Kalimo H;Paetau A;Abramzon Y;Remes AM;Kaganovich A;Scholz SW;Duckworth J;Ding J;Harmer DW;Hernandez DG;Johnson JO;Mok K;Ryten M;Trabzuni D;Guerreiro RJ;Orrell RW;Neal J;Murray A;Pearson J;Jansen IE;Sondervan D;Seelaar H;Blake D;Young K;Halliwell N;Callister JB;Toulson G;Richardson A;Gerhard A;Snowden J;Mann D;Neary D;Nalls MA;Peuralinna T;Jansson L;Isoviita VM;Kaivorinne AL;Hölttä-Vuori M;Ikonen E;Sulkava R;Benatar M;Wuu J;Chiò A;Restagno G;Borghero G;Sabatelli M;ITALSGEN Consortium;Heckerman D;Rogaeva E;Zinman L;Rothstein JD;Sendtner M;Drepper C;Eichler EE;Alkan C;Abdullaev Z;Pack SD;Dutra A;Pak E;Hardy J;Singleton A;Williams NM;Heutink P;Pickering-Brown S;Morris HR;Tienari PJ;Traynor BJ
染色体9p21肌萎缩侧索硬化症-额颞性痴呆(ALS-FTD)基因座包含导致这些常见神经退行性疾病的最后一个主要常染色体显性基因之一。我们之前已经证明，在大多数与该区域相关的病例中，存在涵盖MOBKL2b、IFNK和C9ORF72基因的创建者单倍型。在这里，我们发现在受影响的单倍型上，C9ORF72的第一内含子有一个大的六核苷酸(GGGGCC)重复扩增。这种重复扩增与芬兰人群中的疾病完美分离，在该人群中46.0%的家族性ALS和21.1%的散发性ALS是潜在的。再加上D90A SOD1突变，现在芬兰87%的家族性ALS可以由一个简单的单基因原因解释。重复扩增也出现在三分之一的家族性ALS病例中，这是迄今为止发现的最常见的致命性神经退行性疾病的遗传原因。
The chromosome 9p21 amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) locus contains one of the last major unidentified autosomal dominant genes underlying these common neurodegenerative diseases. We have previously shown that a founder haplotype, covering the MOBKL2b, IFNK and C9ORF72 genes, is present in the majority of cases linked to this region. Here we show that there is a large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 on the affected haplotype. This repeat expansion segregates perfectly with disease in the Finnish population, underlying 46.0% of familial ALS and 21.1% of sporadic ALS in that population. Taken together with the D90A SOD1 mutation, 87% of familial ALS in Finland is now explained by a simple monogenic cause. The repeat expansion is also present in one third of familial ALS cases of outbred European descent making it the most common genetic cause of these fatal neurodegenerative diseases identified to date.
登录
查看更多内容
影响因子：
48
作者：
Laaksovirta, Hannu;Peuralinna, Terhi;Schymick, Jennifer C.;Scholz, Sonja W.;Lai, Shaoi-Lin;Myllykangas, Liisa;Sulkava, Raimo;Jansson, Lilja;Hernandez, Dena G.;Gibbs, J. Raphael;Nalls, Michael A.;Heckerman, David;Tienari, Pentti J.;Traynor, Bryan J.
通讯作者：
Traynor, Bryan J.
影响因子：
56.9
作者：
Kwiatkowski, T. J., Jr.;Bosco, D. A.;Brown, R. H., Jr.
通讯作者：
Brown, R. H., Jr.
影响因子：
6
作者：
Pearson, Justin P.;Williams, Nigel M.;Morris, Huw R.
通讯作者：
Morris, Huw R.
影响因子：
64.8
作者：
ROSEN, DR;SIDDIQUE, T;BROWN, RH
通讯作者：
BROWN, RH
影响因子：
30.8
作者：
Van Deerlin, Vivianna M.;Sleiman, Patrick M. A.;Martinez-Lage, Maria;Chen-Plotkin, Alice;Wang, Li-San;Graff-Radford, Neill R.;Dickson, Dennis W.;Rademakers, Rosa;Boeve, Bradley F.;Grossman, Murray;Arnold, Steven E.;Mann, David M. A.;Pickering-Brown, Stuart M.;Seelaar, Harro;Heutink, Peter;van Swieten, John C.;Murrell, Jill R.;Ghetti, Bernardino;Spina, Salvatore;Grafman, Jordan;Hodges, John;Spillantini, Maria Grazia;Gilman, Sid;Lieberman, Andrew P.;Kaye, Jeffrey A.;Woltjer, Randall L.;Bigio, Eileen H.;Mesulam, Marsel;al-Sarraj, Safa;Troakes, Claire;Rosenberg, Roger N.;White, Charles L., III;Ferrer, Isidro;Llado, Albert;Neumann, Manuela;Kretzschmar, Hans A.;Hulette, Christine Marie;Welsh-Bohmer, Kathleen A.;Miller, Bruce L.;Alzualde, Ainhoa;Lopez de Munain, Adolfo;McKee, Ann C.;Gearing, Marla;Levey, Allan I.;Lah, James J.;Hardy, John;Rohrer, Jonathan D.;Lashley, Tammaryn;Mackenzie, Ian R. A.;Feldman, Howard H.;Hamilton, Ronald L.;Dekosky, Steven T.;van der Zee, Julie;Kumar-Singh, Samir;Van Broeckhoven, Christine;Mayeux, Richard;Vonsattel, Jean Paul G.;Troncoso, Juan C.;Kril, Jillian J.;Kwok, John B. J.;Halliday, Glenda M.;Bird, Thomas D.;Ince, Paul G.;Shaw, Pamela J.;Cairns, Nigel J.;Morris, John C.;McLean, Catriona Ann;DeCarli, Charles;Ellis, William G.;Freeman, Stefanie H.;Frosch, Matthew P.;Growdon, John H.;Perl, Daniel P.;Sano, Mary;Bennett, David A.;Schneider, Julie A.;Beach, Thomas G.;Reiman, Eric M.;Woodruff, Bryan K.;Cummings, Jeffrey;Vinters, Harry V.;Miller, Carol A.;Chui, Helena C.;Alafuzoff, Irina;Hartikainen, Paivi;Seilhean, Danielle;Galasko, Douglas;Masliah, Eliezer;Cotman, Carl W.;Tunon, M. Teresa;Martinez, M. Cristina Caballero;Munoz, David G.;Carroll, Steven L.;Marson, Daniel;Riederer, Peter F.;Bogdanovic, Nenad;Schellenberg, Gerard D.;Hakonarson, Hakon;Trojanowski, John Q.;Lee, Virginia M-Y
通讯作者：
Lee, Virginia M-Y