C9ORF72 repeat expansion in Australian and Spanish frontotemporal dementia patients.
C9ORF72 repeat expansion in Australian and Spanish frontotemporal dementia patients.
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DOI：
10.1371/journal.pone.0056899
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kwok JB
中科院分区：
文献类型：
--
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
C9 ORF 72中的六核苷酸重复扩增已被确定为额颞叶痴呆（FTD）的常见原因。然而，疾病发病机制所需的最小重复数尚不清楚。我们研究的目的是确定两个FTD患者集合（一个澳大利亚和一个西班牙，合并n = 190）中C9 ORF 72重复扩增的频率，检查FTD患者亚组中C9 ORF 72扩增等位基因长度，并检查“非扩增”患者（重复<30）中C9 ORF 72等位基因长度。 在5-17%的患者（家族性FTD患者的21-41%）中检测到C9 ORF 72重复扩增。对于一个家庭来说，这种扩展存在于先证者中，但在68岁时被诊断患有痴呆症的母亲中却不存在。未发现C9 ORF 72非扩展等位基因长度与发病年龄之间存在关联，在西班牙样本中，病例组的平均等位基因长度短于对照组。Southern印迹分析显示，9名“扩增阳性”患者中有一名接受了检查，经神经病理学证实患有TDP-43病理学的额颞叶变性，携带一个平均大小仅为1065个重复的“中间”等位基因。我们的研究表明，C9 ORF 72重复扩增占澳大利亚和西班牙FTD病例的很大比例。然而，C9 ORF 72等位基因长度并不影响研究系列中“非扩展”FTD患者的发病年龄。C9 ORF 72等位基因扩增至少至1065个重复可能足以引起疾病。
A hexanucleotide repeat expansion in C9ORF72 has been established as a common cause of frontotemporal dementia (FTD). However, the minimum repeat number necessary for disease pathogenesis is not known. The aims of our study were to determine the frequency of the C9ORF72 repeat expansion in two FTD patient collections (one Australian and one Spanish, combined n = 190), to examine C9ORF72 expansion allele length in a subset of FTD patients, and to examine C9ORF72 allele length in ‘non-expansion’ patients (those with <30 repeats). The C9ORF72 repeat expansion was detected in 5–17% of patients (21–41% of familial FTD patients). For one family, the expansion was present in the proband but absent in the mother, who was diagnosed with dementia at age 68. No association was found between C9ORF72 non-expanded allele length and age of onset and in the Spanish sample mean allele length was shorter in cases than in controls. Southern blotting analysis revealed that one of the nine ‘expansion-positive’ patients examined, who had neuropathologically confirmed frontotemporal lobar degeneration with TDP-43 pathology, harboured an ‘intermediate’ allele with a mean size of only ∼65 repeats. Our study indicates that the C9ORF72 repeat expansion accounts for a significant proportion of Australian and Spanish FTD cases. However, C9ORF72 allele length does not influence the age at onset of ‘non-expansion’ FTD patients in the series examined. Expansion of the C9ORF72 allele to as little as ∼65 repeats may be sufficient to cause disease.
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影响因子：
2.6
作者：
Schoser B;Timchenko L
通讯作者：
Timchenko L
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：
9.9
作者：
Rohrer, J. D.;Guerreiro, R.;Rossor, M. N.
通讯作者：
Rossor, M. N.
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