Repeat expansions in the C9ORF72 gene contribute to Alzheimer's disease in Caucasians.
Repeat expansions in the C9ORF72 gene contribute to Alzheimer's disease in Caucasians.
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DOI：
10.1016/j.neurobiolaging.2012.10.003
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发表时间：
2013-05
影响因子：
4.2
通讯作者：
Züchner S
中科院分区：
文献类型：
--
作者：
Kohli MA;John-Williams K;Rajbhandary R;Naj A;Whitehead P;Hamilton K;Carney RM;Wright C;Crocco E;Gwirtzman HE;Lang R;Beecham G;Martin ER;Gilbert J;Benatar M;Small GW;Mash D;Byrd G;Haines JL;Pericak-Vance MA;Züchner S
最近，C9ORF72基因的六核苷酸重复扩增已被确定为受额颞叶痴呆（FTD）和肌萎缩侧索硬化症（ALS）影响的高加索家族的重要部分。鉴于FTD与阿尔茨海默病（AD）的临床重叠，我们假设C9ORF72扩增可能与AD有关。在白种人中，我们发现C9ORF72扩增在FTD/ALS的致病范围内（bbb30重复），AD病例的扩增率为0.76%，而对照组为零（p=3.3E-03, 1182例，1039例对照）。相比之下，在非裔美国人个体（291例，620例对照）中未发现大的扩张。然而，在C9ORF72扩增的正常变异范围内（0-23个重复拷贝），我们发现白种人和非裔美国人在分布和平均重复计数上存在显著差异。对已鉴定的C9ORF72扩增载体的临床和病理重新评估显示，9例临床和/或尸检证实AD， 2例最终诊断为FTD。因此，我们的研究结果支持了C9ORF72大量扩增导致包括阿尔茨海默病在内的神经退行性疾病表型谱的观点。
Recently, a hexanucleotide repeat expansion in the C9ORF72 gene has been identified to account for a significant portion of Caucasian families affected by frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Given the clinical overlap of FTD with Alzheimer disease (AD), we hypothesized that C9ORF72 expansions may contribute to AD. In Caucasians, we found C9ORF72 expansions in the pathogenic range of FTD/ALS (>30 repeats) at a rate of 0.76% in AD cases versus zero in controls (p=3.3E-03, 1,182 cases, 1,039 controls). In contrast, no large expansions were detected in individuals of African American ethnicity (291 cases, 620 controls). However, in the range of normal variation of C9ORF72 expansions (0–23 repeat copies), we detected significant differences in distribution and mean repeat counts between Caucasians and African Americans. Clinical and pathological reevaluation of identified C9ORF72 expansion carriers revealed nine clinical and/or autopsy confirmed AD and two FTD finial diagnoses. Thus, our results support the notion that large C9ORF72 expansions lead to a phenotypic spectrum of neurodegenerative disease including AD.
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DOI：
10.1016/s1474-4422(12)70043-1
发表时间：
2012-04
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Majounie E;Renton AE;Mok K;Dopper EG;Waite A;Rollinson S;Chiò A;Restagno G;Nicolaou N;Simon-Sanchez J;van Swieten JC;Abramzon Y;Johnson JO;Sendtner M;Pamphlett R;Orrell RW;Mead S;Sidle KC;Houlden H;Rohrer JD;Morrison KE;Pall H;Talbot K;Ansorge O;Chromosome 9-ALS/FTD Consortium;French research network on FTLD/FTLD/ALS;ITALSGEN Consortium;Hernandez DG;Arepalli S;Sabatelli M;Mora G;Corbo M;Giannini F;Calvo A;Englund E;Borghero G;Floris GL;Remes AM;Laaksovirta H;McCluskey L;Trojanowski JQ;Van Deerlin VM;Schellenberg GD;Nalls MA;Drory VE;Lu CS;Yeh TH;Ishiura H;Takahashi Y;Tsuji S;Le Ber I;Brice A;Drepper C;Williams N;Kirby J;Shaw P;Hardy J;Tienari PJ;Heutink P;Morris HR;Pickering-Brown S;Traynor BJ
通讯作者：
Traynor BJ
影响因子：
3.7
作者：
Cruchaga C;Haller G;Chakraverty S;Mayo K;Vallania FL;Mitra RD;Faber K;Williamson J;Bird T;Diaz-Arrastia R;Foroud TM;Boeve BF;Graff-Radford NR;St Jean P;Lawson M;Ehm MG;Mayeux R;Goate AM;NIA-LOAD/NCRAD Family Study Consortium
通讯作者：
NIA-LOAD/NCRAD Family Study Consortium
影响因子：
14.5
作者：
Chio, Adriano;Borghero, Giuseppe;Sabatelli, Mario
通讯作者：
Sabatelli, Mario
具有额颞叶变性的谱系 - 运动神经元疾病和焦油DNA结合蛋白-43阳性神经病理学：与9号染色体的遗传联系。
影响因子：
2.6
作者：
Luty, Agnes A.;Kwok, John B. J.;Thompson, Elizabeth M.;Blumbergs, Peter;Brooks, William S.;Loy, Clement T.;Dobson-Stone, Carol;Panegyres, Peter K.;Hecker, Jane;Nicholson, Garth A.;Halliday, Glenda M.;Schofield, Peter R.
通讯作者：
Schofield, Peter R.
影响因子：
12.7
作者：
Murray ME;DeJesus-Hernandez M;Rutherford NJ;Baker M;Duara R;Graff-Radford NR;Wszolek ZK;Ferman TJ;Josephs KA;Boylan KB;Rademakers R;Dickson DW
通讯作者：
Dickson DW