|
Hemimegalencephaly
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Somatic gain-of-function variants in MTOR and its activators (AKT3, PIK3CA, RHEB), as well as germline, somatic and two-hit loss-of-function variants in its repressors (DEPDC5, TSC1, TSC2) were found exclusively in FCD2/HME cases.
|
31444548 |
2019 |
|
Hemimegalencephaly
|
0.500 |
Biomarker
|
disease |
BEFREE |
Somatic double-hit in MTOR and RPS6 in hemimegalencephaly with intractable epilepsy.
|
31411685 |
2019 |
|
Hemimegalencephaly
|
0.500 |
Biomarker
|
disease |
BEFREE |
Germline and somatic mutation in genes belonging to the Mammalian Target of Rapamycin (mTOR) pathway has been identified in patients suffering from epilepsy secondary to Hemimegalencephaly and focal cortical dysplasia.
|
30414531 |
2019 |
|
Hemimegalencephaly
|
0.500 |
Biomarker
|
disease |
BEFREE |
Mutations in single genes encoding mTOR pathway regulatory proteins have been linked to MCD such as focal cortical dysplasia (FCD) types IIa and IIb, hemimegalencephaly (HME), and megalencephaly.
|
31625153 |
2019 |
|
Hemimegalencephaly
|
0.500 |
Biomarker
|
disease |
BEFREE |
Over the last decade, there has been increasing evidence that hyperactivation of the mechanistic target of rapamycin (mTOR) pathway is a hallmark of malformations of cortical development such as focal cortical dysplasia (FCD) or hemimegalencephaly.
|
29359340 |
2018 |
|
Hemimegalencephaly
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
We suspect cell-autonomous migration arrest on the radial glial foot by the active MTOR mutation and offer potential explanations for why this may lead to cortical malformations such as HME.
|
28427592 |
2017 |
|
Hemimegalencephaly
|
0.500 |
Biomarker
|
disease |
BEFREE |
Mutations of genes within the phosphatidylinositol-3-kinase (PI3K)-AKT-MTOR pathway are well known causes of brain overgrowth (megalencephaly) as well as segmental cortical dysplasia (such as hemimegalencephaly, focal cortical dysplasia and polymicrogyria).
|
28969385 |
2017 |
|
Hemimegalencephaly
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Brain somatic mutations in the gene encoding mTOR (MTOR) have recently been linked to focal cortical dysplasia and other associated brain pathologies including hemimegalencephaly.
|
27323939 |
2016 |
|
Hemimegalencephaly
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
While somatic MTOR mutations have been recognized in tumors for many years, and more recently in hemimegalencephaly, germline MTOR mutations have rarely been described.
|
26542245 |
2015 |
|
Hemimegalencephaly
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Mutations in mTOR regulatory genes (e.g., TSC1, TSC2, AKT3, DEPDC5) have been associated with several focal MCD highly associated with epilepsy such as tuberous sclerosis complex (TSC), hemimegalencephaly (HME; brain malformation associated with dramatic enlargement of one brain hemisphere), and cortical dysplasia. mTOR plays important roles in the regulation of cell division, growth, and survival, and, thus, aberrant activation of the cascade during cortical development can cause dramatic alterations in cell size, cortical lamination, and axon and dendrite outgrowth often observed in focal MCD.
|
25833943 |
2015 |
|
Hemimegalencephaly
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Mammalian target of rapamycin pathway mutations cause hemimegalencephaly and focal cortical dysplasia.
|
25599672 |
2015 |
|
Hemimegalencephaly
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
The studies reviewed suggest that somatic mutations of the PI3K-AKT-mTOR pathway limited to the brain may represent one cause of HME.
|
23449172 |
2013 |
|
Hemimegalencephaly
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
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.
|
22729223 |
2012 |
|
Hemimegalencephaly
|
0.500 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
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.
|
22729223 |
2012 |
|
Hemimegalencephaly
|
0.500 |
AlteredExpression
|
disease |
BEFREE |
The cellular mechanism and significance of P-S6-specific activation of the mTOR cascade in HME, particularly in the inflammatory cell lineage, should be explored further.
|
19804889 |
2009 |
|
Hemimegalencephaly
|
0.500 |
Biomarker
|
disease |
HPO |
|
|
|
|
Hemimegalencephaly
|
0.500 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
|
|
|
|
Hemimegalencephaly
|
0.500 |
CausalMutation
|
disease |
CLINVAR |
|
|
|