Screening a UK amyotrophic lateral sclerosis cohort provides evidence of multiple origins of the C9orf72 expansion.
Screening a UK amyotrophic lateral sclerosis cohort provides evidence of multiple origins of the C9orf72 expansion.
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DOI：
10.1016/j.neurobiolaging.2014.07.037
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发表时间：
2015-01
影响因子：
4.2
通讯作者：
Fisher EM
中科院分区：
文献类型：
--
作者：
Fratta P;Polke JM;Newcombe J;Mizielinska S;Lashley T;Poulter M;Beck J;Preza E;Devoy A;Sidle K;Howard R;Malaspina A;Orrell RW;Clarke J;Lu CH;Mok K;Collins T;Shoaii M;Nanji T;Wray S;Adamson G;Pittman A;Renton AE;Traynor BJ;Sweeney MG;Revesz T;Houlden H;Mead S;Isaacs AM;Fisher EM
C9 orf 72基因中的扩展六核苷酸重复序列是肌萎缩侧索硬化症和额颞叶痴呆（C9 ALS/FTD）的最常见遗传原因。虽然一般人群中存在0-30个六核苷酸重复，但>500个重复的扩增与C9 ALS/FTD相关。大的C9 ALS/FTD扩增共享一个共同的单倍型，这些扩增是否来源于单一的创始人或更频繁地发生在易感单倍型上尚未确定，并且与疾病病理机制相关。此外，尽管已经描述了携带50-200个重复的病例，但它们的作用和扩增的致病阈值仍有待确定，并且对于诊断和遗传咨询具有重要意义。我们目前的临床和遗传数据从英国ALS队列和报告的详细分子研究的非典型体细胞不稳定的扩展90个重复。我们在不同组织中的研究结果为这种重复数的致病性提供了证据，表明它们可以在中枢神经系统中体细胞扩展到充分表征的致病范围。我们的结果支持C9 ALS/FTD发生多个扩增事件。
An expanded hexanucleotide repeat in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). Although 0–30 hexanucleotide repeats are present in the general population, expansions >500 repeats are associated with C9ALS/FTD. Large C9ALS/FTD expansions share a common haplotype and whether these expansions derive from a single founder or occur more frequently on a predisposing haplotype is yet to be determined and is relevant to disease pathomechanisms. Furthermore, although cases carrying 50–200 repeats have been described, their role and the pathogenic threshold of the expansions remain to be identified and carry importance for diagnostics and genetic counseling. We present clinical and genetic data from a UK ALS cohort and report the detailed molecular study of an atypical somatically unstable expansion of 90 repeats. Our results across different tissues provide evidence for the pathogenicity of this repeat number by showing they can somatically expand in the central nervous system to the well characterized pathogenic range. Our results support the occurrence of multiple expansion events for C9ALS/FTD.
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影响因子：
3.7
作者：
Dobson-Stone C;Hallupp M;Loy CT;Thompson EM;Haan E;Sue CM;Panegyres PK;Razquin C;Seijo-Martínez M;Rene R;Gascon J;Campdelacreu J;Schmoll B;Volk AE;Brooks WS;Schofield PR;Pastor P;Kwok JB
通讯作者：
Kwok JB
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：
3.5
作者：
Dols-Icardo, Oriol;Garcia-Redondo, Alberto;Clarimon, Jordi
通讯作者：
Clarimon, Jordi
影响因子：
9.9
作者：
van Blitterswijk, Marka;Baker, Matthew C.;Rademakers, Rosa
通讯作者：
Rademakers, Rosa
影响因子：
9.9
作者：
Moss, Davina J. Hensman;Poulter, Mark;Tabrizi, Sarah J.
通讯作者：
Tabrizi, Sarah J.