Dissecting the genetic basis of focal cortical dysplasia: a large cohort study.

Baldassari S, Ribierre T, Marsan E, Adle-Biassette H, Ferrand-Sorbets S, Bulteau C, Dorison N, Fohlen M, Polivka M, Weckhuysen S, Dorfmüller G, …, Baulac S · 2019 · Acta Neuropathologica · Atlas ID BAL2019

What this study shows

In 80 children operated for drug-resistant epilepsy, deep sequencing of brain and matched blood found brain-restricted gain-of-function variants in mTOR-pathway activators (MTOR, AKT3, PIK3CA and RHEB) only in focal cortical dysplasia type 2 (FCD2) and hemimegalencephaly (HME): 29 of 62 cases (47%). Loss-of-function variants in repressors (DEPDC5, TSC1, TSC2) were found in FCD2 as well. All 25 FCD2 cases examined showed strong pS6 staining, a readout of mTOR activity, in dysmorphic neurons and balloon cells, including cases with no variant found. RHEB is one of four activator genes reported here; the RHEB-specific case count sits in the paper's tables and is not recorded in this entry. Observational, single centre, and the variants were not tested for function in this paper.

Abstract

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Genetic malformations of cortical development (MCDs), such as mild MCDs (mMCD), focal cortical dysplasia (FCD), and hemimegalencephaly (HME), are major causes of severe pediatric refractory epilepsies subjected to neurosurgery. FCD2 are characterized by neuropathological hallmarks that include enlarged dysmorphic neurons (DNs) and balloon cells (BCs). Here, we provide a comprehensive assessment of the contribution of germline and somatic variants in a large cohort of surgical MCD cases.

Read the full abstract on PubMed →

At a glance

Evidence type	H Human study Marked H because it is direct evidence from a human clinical trial or human cohort; the code names the kind of study, not its quality -- a small, well-run trial is still H.
Study type	3 - Human Observational
Model system	Human (80 children with drug-resistant epilepsy; post-surgical brain tissue with matched blood)
Journal	Acta Neuropathologica
Year	2019
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1007/s00401-019-02061-5 · PMID 31444548 · Free full text (PMC6851393)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	None (observational genetic cohort)
Target	mTOR pathway activators (MTOR, AKT3, PIK3CA, RHEB) and repressors (DEPDC5, TSC1, TSC2)
Model	Human
Effect	Somatic gain-of-function activator variants in FCD2/HME; strong pS6 in dysmorphic neurons and balloon cells
Sample size	80 children enrolled; 29 of 62 FCD2/HME cases carried an activator variant; 25 FCD2 cases analysed for pS6
Limitations	Single centre. Observational: variants not functionally tested here. pS6 is a downstream readout. RHEB-specific case count and allele frequencies were not extracted (gene names were lost in the text conversion); see the paper's tables.

In the Atlas

Links in the pathway map

Supports Rheb activates mTORC1

Cite this paper

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Baldassari, S., Ribierre, T., Marsan, E., Adle-Biassette, H., Ferrand-Sorbets, S., Bulteau, C., Dorison, N., Fohlen, M., Polivka, M., Weckhuysen, S., Dorfmüller, G., Chipaux, M., & Baulac, S. (2019). Dissecting the genetic basis of focal cortical dysplasia: a large cohort study. Acta Neuropathologica. https://doi.org/10.1007/s00401-019-02061-5

@article{BAL2019,
  author       = {Baldassari, S. and Ribierre, T. and Marsan, E. and Adle-Biassette, H. and Ferrand-Sorbets, S. and Bulteau, C. and Dorison, N. and Fohlen, M. and Polivka, M. and Weckhuysen, S. and Dorfmüller, G. and Chipaux, M. and Baulac, S.},
  title        = {{Dissecting the genetic basis of focal cortical dysplasia: a large cohort study}},
  journal      = {Acta Neuropathologica},
  year         = {2019},
  doi          = {10.1007/s00401-019-02061-5},
  note         = {PMID: 31444548},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record BAL2019) [Data set]. https://mtor-atlas.org/study/BAL2019/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_BAL2019,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record BAL2019},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/BAL2019/},
  doi          = {10.5281/zenodo.22059963}
}

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