Profilin1 E117G is a moderate risk factor for amyotrophic lateral sclerosis.
Profilin1 E117G is a moderate risk factor for amyotrophic lateral sclerosis.
复制标题
DOI：
10.1136/jnnp-2013-306761
复制
发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
Fisher EM
中科院分区：
文献类型：
--
作者：
Fratta P;Charnock J;Collins T;Devoy A;Howard R;Malaspina A;Orrell R;Sidle K;Clarke J;Shoai M;Lu CH;Hardy J;Plagnol V;Fisher EM
肌萎缩性侧索硬化症（ALS）和额颞叶痴呆（FTD）是进行性神经退行性疾病，具有显著的临床、病理和遗传重叠，被认为是一种常见疾病谱系的不同末端。Profilin1的突变最近被描述为家族性ALS的罕见原因。PFN1 E117G错义变异已在家族性和散发病例中发现，在对照中也发现，这使人们对其致病性产生怀疑。这些变异的解释是一个重大的临床遗传学挑战。在这里，我们将383名ALS患者的新队列筛选与多序列数据集相结合，以完善PFN1 E117G相关的ALS和FTD风险的估计。我们的队列总共有5118例ALS和FTD病例和13089例对照。我们估计对照组中E117G的频率为0.11%，病例中为0.25%。总体分层后的估计赔率为2.44 （95% CI 1.048 to∞，Mantel-Haenszel检验p=0.036）。我们的研究结果显示E117G与ALS之间存在关联，且效应大小适中。
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive neurodegenerative disorders that share significant clinical, pathological and genetic overlap and are considered to represent different ends of a common disease spectrum. Mutations in Profilin1 have recently been described as a rare cause of familial ALS. The PFN1 E117G missense variant has been described in familial and sporadic cases, and also found in controls, casting doubt on its pathogenicity. Interpretation of such variants represents a significant clinical-genetics challenge. Here, we combine a screen of a new cohort of 383 ALS patients with multiple-sequence datasets to refine estimates of the ALS and FTD risk associated with PFN1 E117G. Together, our cohorts add up to 5118 ALS and FTD cases and 13 089 controls. We estimate a frequency of E117G of 0.11% in controls and 0.25% in cases. Estimated odds after population stratification is 2.44 (95% CI 1.048 to ∞, Mantel-Haenszel test p=0.036). Our results show an association between E117G and ALS, with a moderate effect size.
登录
查看更多内容
DOI：
10.3109/21678421.2013.787630
发表时间：
2013-09
影响因子：
2.8
作者：
van Blitterswijk M;Baker MC;Bieniek KF;Knopman DS;Josephs KA;Boeve B;Caselli R;Wszolek ZK;Petersen R;Graff-Radford NR;Boylan KB;Dickson DW;Rademakers R
通讯作者：
Rademakers R
影响因子：
64.8
作者：
Wu, Chi-Hong;Fallini, Claudia;Ticozzi, Nicola;Keagle, Pamela J.;Sapp, Peter C.;Piotrowska, Katarzyna;Lowe, Patrick;Koppers, Max;McKenna-Yasek, Diane;Baron, Desiree M.;Kost, Jason E.;Gonzalez-Perez, Paloma;Fox, Andrew D.;Adams, Jenni;Taroni, Franco;Tiloca, Cinzia;Leclerc, Ashley Lyn;Chafe, Shawn C.;Mangroo, Dev;Moore, Melissa J.;Zitzewitz, Jill A.;Xu, Zuo-Shang;van den Berg, Leonard H.;Glass, Jonathan D.;Siciliano, Gabriele;Cirulli, Elizabeth T.;Goldstein, David B.;Salachas, Francois;Meininger, Vincent;Rossoll, Wilfried;Ratti, Antonia;Gellera, Cinzia;Bosco, Daryl A.;Bassell, Gary J.;Silani, Vincenzo;Drory, Vivian E.;Brown, Robert H., Jr.;Landers, John E.
通讯作者：
Landers, John E.
影响因子：
4.2
作者：
Ingre, Caroline;Landers, John E.;Weishaupt, Jochen H.
通讯作者：
Weishaupt, Jochen H.
影响因子：
14.5
作者：
HAVERKAMP, LJ;APPEL, V;APPEL, SH
通讯作者：
APPEL, SH
影响因子：
3.5
作者：
van Blitterswijk, Marka;van Es, Michael A.;van den Berg, Leonard H.
通讯作者：
van den Berg, Leonard H.