Investigation of c9orf72 in 4 neurodegenerative disorders.
Investigation of c9orf72 in 4 neurodegenerative disorders.
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DOI：
10.1001/archneurol.2012.2016
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发表时间：
2012-12
影响因子：
--
通讯作者：
Rogaeva, Ekaterina
中科院分区：
文献类型：
--
作者：
Xi, Zhengrui;Zinman, Lorne;Grinberg, Yakov;Moreno, Danielle;Sato, Christine;Bilbao, Juan M.;Ghani, Mahdi;Hernandez, Isabel;Ruiz, Agustin;Boada, Merce;Moron, Francisco J.;Lang, Anthony E.;Marras, Connie;Bruni, Amalia;Colao, Rosanna;Maletta, Raffaele G.;Puccio, Gianfranco;Rainero, Innocenzo;Pinessi, Lorenzo;Galimberti, Daniela;Morrison, Karen E.;Moorby, Catriona;Stockton, Joanne D.;Masellis, Mario;Black, Sandra E.;Hazrati, Lili-Naz;Liang, Yan;de With, Jan van Haersma;Fornazzari, Luis;Villagra, Roque;Rojas-Garcia, Ricardo;Clarimon, Jordi;Mayeux, Richard;Robertson, Janice;St George-Hyslop, Peter;Rogaeva, Ekaterina
目的：评估肌萎缩侧索硬化症（ALS）、额颞叶变性（FTLD）、阿尔茨海默病（AD）和帕金森病（PD）患者C9 orf 72（G4 C2）重复序列的等位基因频率。通过2步基因分型策略估计重复数。对于扩增携带者，我们对重复侧翼区进行测序，获得APOE基因型和MAPT H1/H2单倍型。专门治疗神经退行性疾病的医院。我们分析了520例FTLD患者，389例ALS患者，424例AD患者，289例PD患者，602例对照，18个家族和29例LRRK 2 G2019 S突变的PD患者。扩展频率。基于先前的截止值（>30次重复），在9.3%的ALS患者、5.2%的FTLD患者和0.7%的PD患者中检测到扩增，但在对照组或AD患者中未检测到扩增。它与ALS或FTLD家族史和FTLD发病年龄显著相关。表型变异（ALS vs FTLD）与MAPT、APOE或重复侧翼区变异无关。2例PD患者是39和32重复的携带者，具有可疑的病理学意义，因为39重复等位基因不与PD分离。在G2019 S携带者和TAR DNA结合蛋白43阳性包涵体的AD病例中未发现扩增或中间等位基因（20-29个重复）。令人惊讶的是，与对照组相比，所有4种神经退行性疾病中10重复等位基因的频率略有增加，表明C9 orf 72基因座存在未知的风险变异。C9 orf 72扩增是ALS和FTLD的常见原因，但不是AD或PD的常见原因。我们的研究引起了对病理重复数的可靠截止值的关注，这在遗传筛查的实用性中很重要。
To estimate the allele frequency of C9orf72 (G4C2) repeats in amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Alzheimer disease (AD), and Parkinson disease (PD). The number of repeats was estimated by a 2-step genotyping strategy. For expansion carriers, we sequenced the repeat flanking regions and obtained APOE genotypes and MAPT H1/H2 haplotypes. Hospitals specializing in neurodegenerative disorders. We analyzed 520 patients with FTLD, 389 patients with ALS, 424 patients with AD, 289 patients with PD, 602 controls, 18 families, and 29 patients with PD with the LRRK2 G2019S mutation. The expansion frequency. Based on a prior cutoff (>30 repeats), the expansion was detected in 9.3% of patients with ALS, 5.2% of patients with FTLD, and 0.7% of patients with PD but not in controls or patients with AD. It was significantly associated with family history of ALS or FTLD and age at onset of FTLD. Phenotype variation (ALS vs FTLD) was not associated with MAPT, APOE, or variability in the repeat flanking regions. Two patients with PD were carriers of 39 and 32 repeats with questionable pathological significance, since the 39-repeat allele does not segregate with PD. No expansion or intermediate alleles (20–29 repeats) were found among the G2019S carriers and AD cases with TAR DNA-binding protein 43–positive inclusions. Surprisingly, the frequency of the 10-repeat allele was marginally increased in all 4 neurodegenerative diseases compared with controls, indicating the presence of an unknown risk variation in the C9orf72 locus. The C9orf72 expansion is a common cause of ALS and FTLD, but not of AD or PD. Our study raises concern about a reliable cutoff for the pathological repeat number, which is important in the utility of genetic screening.
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DOI：
10.4088/jcp.08m04476
发表时间：
2009-06
期刊：
The Journal of clinical psychiatry
影响因子：
--
作者：
Bourgeois JA;Coffey SM;Rivera SM;Hessl D;Gane LW;Tassone F;Greco C;Finucane B;Nelson L;Berry-Kravis E;Grigsby J;Hagerman PJ;Hagerman RJ
通讯作者：
Hagerman RJ
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：
9.9
作者：
Paisán-Ruíz, C;Lang, AE;Rogaeva, E
通讯作者：
Rogaeva, E
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：
4.2
作者：
Bernardi, L;Maletta, RG;Bruni, AC
通讯作者：
Bruni, AC