1 100

Cited 0 times in

De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly

Authors
 Jeong Ho Lee  ;  My Huynh  ;  Jennifer L Silhavy  ;  Sangwoo Kim  ;  Tracy Dixon-Salazar  ;  Andrew Heiberg  ;  Eric Scott  ;  Vineet Bafna  ;  Kiley J Hill  ;  Adrienne Collazo  ;  Vincent Funari  ;  Carsten Russ  ;  Stacey B Gabriel  ;  Gary W Mathern & Joseph G Gleeson 
Citation
 Nature Genetics, Vol.44(8) : 941-945, 2012 
Journal Title
 Nature Genetics 
ISSN
 1061-4036 
Issue Date
2012
Abstract
De novo somatic mutations in focal areas are well documented in diseases such as neoplasia but are rarely reported in malformation of the developing brain. Hemimegalencephaly (HME) is characterized by overgrowth of either one of the two cerebral hemispheres. The molecular etiology of HME remains a mystery. The intractable epilepsy that is associated with HME can be relieved by the surgical treatment hemispherectomy, allowing sampling of diseased tissue. Exome sequencing and mass spectrometry analysis in paired brain-blood samples from individuals with HME (n = 20 cases) identified de novo somatic mutations in 30% of affected individuals in the PIK3CA, AKT3 and MTOR genes. A recurrent PIK3CA c.1633G>A mutation was found in four separate cases. Identified mutations were present in 8-40% of sequenced alleles in various brain regions and were associated with increased neuronal S6 protein phosphorylation in the brains of affected individuals, indicating aberrant activation of mammalian target of rapamycin (mTOR) signaling. Thus HME is probably a genetically mosaic disease caused by gain of function in phosphatidylinositol 3-kinase (PI3K)-AKT3-mTOR signaling.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91504
DOI
10.1038/ng.2329
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부)
Yonsei Authors
김상우(Kim, Sang Woo)
사서에게 알리기
  feedback
Full Text
http://www.nature.com/ng/journal/v44/n8/full/ng.2329.html
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse