期刊
NEURON
卷 74, 期 1, 页码 41-48出版社
CELL PRESS
DOI: 10.1016/j.neuron.2012.03.010
关键词
-
资金
- American Academy of Neurology
- Milken Family Foundation
- American Epilepsy Society
- NINDS [K23NS069784, K99/R00, R00 NS072192, K08 NS047213, R01 NS35129, RO1 NS032457]
- Shore Fellowship
- NCI [P01 CA142536]
- Sontag Foundation
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 two out of eight HMG samples showed trisomy of chromosome 1q, which encompasses many genes, including AKT3, a gene 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 paralog in the brain during neurogenesis and that phosphorylated AKT is abundant in cortical progenitor cells. Our data suggest that somatic mutations limited to the brain could represent an important cause of complex neurogenetic disease.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据