Somatic activation of AKT3 causes hemispheric developmental brain malformations.
Somatic activation of AKT3 causes hemispheric developmental brain malformations.
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DOI：
10.1016/j.neuron.2012.03.010
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发表时间：
2012-04-12
期刊：
影响因子：
16.2
通讯作者：
Walsh CA
中科院分区：
文献类型：
--
作者：
Poduri A;Evrony GD;Cai X;Elhosary PC;Beroukhim R;Lehtinen MK;Hills LB;Heinzen EL;Hill A;Hill RS;Barry BJ;Bourgeois BF;Riviello JJ;Barkovich AJ;Black PM;Ligon KL;Walsh CA
Hemimegalencephaly（HMG）是一种发育性的脑部疾病，其特征是畸形的脑半球，通常会导致癫痫病，需要手术切除，我们研究了HMG组织以测试该状况是否反映了对大脑发育至关重要的体细胞突变2/8 HMG样品显示了1q染色体的三体，包括许多基因，包括Akt3，已知可以调节大脑大小。在患者的血细胞中不存在，Akt3中的E17K突变与Akt1的E17K突变完全相同，而Akt2和Akt2最近在体细胞过度生长综合征中发现了AKT3。在皮质祖细胞中是绝对的，我们的数据表明，限制在大脑的体细胞可能是复杂的神经遗传疾病的重要原因。
Hemimegalencephaly (HMG) is a developmental brain disorder characterized by an enlarged, malformed cerebral hemisphere, typically causing epilepsy that requires surgical resection. We studied resected HMG tissue to test whether the condition might reflect somatic mutations affecting genes critical to brain development. We found that 2/8 HMG samples showed trisomy of chromosome 1q, encompassing many genes, including AKT3, which is known to regulate brain size. A third case showed a known activating mutation in AKT3 (c.49G→A, creating p.E17K) that was not present in the patient’s blood cells. Remarkably, the E17K mutation in AKT3 is exactly paralogous to E17K mutations in AKT1 and AKT2 recently discovered in somatic overgrowth syndromes. We show that AKT3 is the most abundant AKT paralogue in brain during neurogenesis and that phosphorylated AKT is abundant in cortical progenitor cells. Our data suggest that somatic mutations limited to brain could represent an important cause of complex neurogenetic disease.
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影响因子：
8.8
作者：
Davies, M. A.;Stemke-Hale, K.;Tellez, C.;Calderone, T. L.;Deng, W.;Prieto, V. G.;Lazar, A. J. F.;Gershenwald, J. E.;Mills, G. B.
通讯作者：
Mills, G. B.
影响因子：
1.9
作者：
Flores-Sarnat, L;Sarnat, HB;Alvarez, A
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Alvarez, A
宇宙（癌症中的体细胞突变目录）数据库和网站。
影响因子：
8.8
作者：
Bamford, S;Dawson, E;Forbes, S;Clements, J;Pettett, R;Dogan, A;Flanagan, A;Teague, J;Futreal, PA;Stratton, MR;Wooster, R
通讯作者：
Wooster, R
影响因子：
30.8
作者：
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Lee, C
影响因子：
64.8
作者：
Muotri, Alysson R.;Gage, Fred H.
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