ArticleNature genetics2012
De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly.
Article in Nature genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 345 papers, 2 of them syntheses that pooled it.
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Who cites it
345 citing papers in PubMed, 2 syntheses or guidelines pooled it, 691 citations in OpenAlex.
- Genome-wide meta-analysis of brain volume identifies genomic loci and genes shared with intelligence.Nature communications · 2020Pooled it
- Genotype-phenotype correlations in focal malformations of cortical development: a pathway to integrated pathological diagnosis in epilepsy surgery.Brain pathology (Zurich, Switzerland) · 2019Pooled it
- Clinical experience with the AKT1 inhibitor miransertib in two children with PIK3CA-related overgrowth syndrome.Orphanet journal of rare diseases · 2021Trial
- HOPX regulates the development and lineage progression of human stem cell-derived outer radial glia-like cells.Stem cell reports · 2026Article
- Ras-MAPK somatic variants in mesial temporal lobe epilepsy.Current opinion in genetics & development · 2026Review
- Somatic mosaicism in the brain: linking development, ageing and neurodegeneration.Nature reviews. Neurology · 2026Review
- Focal Cortical Dysplasia Type II: Somatic Mutations, Molecular Mechanisms, and Integrative Multi-Omics Framework.CNS neuroscience & therapeutics · 2026Review
- Article
- Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE): genetics, mechanisms and precision therapy.Acta neuropathologica · 2026Review
- Genetic testing and analysis of 1024 children with global developmental delay or intellectual disability: a single-center cohort study.European journal of pediatrics · 2026Article
- Single-nucleus RNA sequencing reveals ferroptosis as a potential contributor to the pathogenesis of focal cortical dysplasia.Clinical and translational medicine · 2026Article
- Disease insights from brain somatic mosaicism.Experimental & molecular medicine · 2026Review
- Activating Ras-MAPK pathway variants drive hippocampal clonal competition in human epilepsy.bioRxiv : the preprint server for biology · 2026Article
- Epileptogenesis and Epilepsy Treatment: Advances in Mechanistic Understanding, Therapeutic Approaches, and Future Perspectives.International journal of molecular sciences · 2026Review
- Prenatal Diagnosis of Malformations of Cortical Development: A Review of Genetic and Imaging Advances.Biomedicines · 2026Review
- Case Report: Whole-genome sequencing of urothelial carcinoma in an adult patient with CLOVES syndrome reveals a lack ofFrontiers in oncology · 2026Article
- Fetal Macrocephaly: Prenatal Findings and Follow-Up in Cases With High Risk for Abnormal Outcome.Prenatal diagnosis · 2026Article
- Genetic Insights in Hindbrain Abnormalities Through Network Analysis Expose Key Biological Pathways in Hindbrain Development.Cerebellum (London, England) · 2025Article
- Early death and neuronal abnormalities inbioRxiv : the preprint server for biology · 2025Article
- SLC35A2 loss-of-function variants affect glycomic signatures, neuronal fate and network dynamics.Brain : a journal of neurology · 2025Article
285 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 1 country.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.