The MAPT p.A152T variant is a risk factor associated with tauopathies with atypical clinical and neuropathological features.
The MAPT p.A152T variant is a risk factor associated with tauopathies with atypical clinical and neuropathological features.
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DOI：
10.1016/j.neurobiolaging.2012.04.006
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发表时间：
2012-09
影响因子：
4.2
通讯作者：
Revesz T
中科院分区：
文献类型：
--
作者：
Kara E;Ling H;Pittman AM;Shaw K;de Silva R;Simone R;Holton JL;Warren JD;Rohrer JD;Xiromerisiou G;Lees A;Hardy J;Houlden H;Revesz T
微管相关蛋白tau（MAPT）突变已被证明是额颞叶痴呆和各种其他散发性tau蛋白病的基础。我们发现了一种罕见的p.A152T变异的MAPT外显子7在两个（8）患者的临床表现帕金森综合征和尸检发现的神经系统缠结病理。一名患者的两个兄弟姐妹也携带p.A152T变异，并且都有进行性认知障碍。进一步的筛查在另外两个病例中发现了这种变异：一个病例经病理证实为皮质基底节变性，另一个病例诊断为帕金森病伴痴呆。证据的平衡表明，这种变异与疾病有关，但突变病例的表型差异很大，这与它是一种完全渗透的致病突变不一致。有趣的是，这种变异导致产生一个新的磷酸化位点，可能导致微管结合减少。我们认为，A152T变异是一个危险因素，与发展的非典型神经退行性疾病与异常tau积累。
Microtubule-associated protein tau (MAPT) mutations have been shown to underlie frontotemporal dementia and a variety of additional sporadic tauopathies. We identified a rare p.A152T variant in MAPT exon 7 in two (of eight) patients with clinical presentation of parkinsonism and postmortem finding of neurofibrillary tangle pathology. Two siblings of one patient also carried the p.A152T variant, and both have progressive cognitive impairment. Further screening identified the variant in two other cases: one with pathologically confirmed corticobasal degeneration and another with the diagnosis of Parkinson's disease with dementia. The balance of evidence suggests this variant is associated with disease, but the very varied phenotype of the cases with the mutation is not consistent with it being a fully penetrant pathogenic mutation. Interestingly, this variation results in the creation of a new phosphorylation site that could cause reduced microtubule binding. We suggest that the A152T variant is a risk factor associated with the development of atypical neurodegenerative conditions with abnormal tau accumulation.
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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：
8.6
作者：
Caparros-Lefebvre, Dominique;Steele, John;Ohta, Shigeru
通讯作者：
Ohta, Shigeru
影响因子：
16.2
作者：
Paisán-Ruíz, C;Jain, S;Singleton, AB
通讯作者：
Singleton, AB
影响因子：
8.6
作者：
Steele, JC
通讯作者：
Steele, JC
影响因子：
3.9
作者：
Tan, Eng-King;Peng, Rong;Wu, Ruey-Meei
通讯作者：
Wu, Ruey-Meei