Ras-MAPK somatic variants in mesial temporal lobe epilepsy.

Siena Cono, Kristopher T Kahle, Christopher A Walsh, Sattar Khoshkhoo

Abstract readReview

In one paragraph

Review in Current opinion in genetics & development, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

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0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Siena ConoDepartment of Neurology, Mass General Brigham, Harvard Medical School, Boston, MA, USA.

Kristopher T KahleDivision of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Neurosurgery, Mass General Brigham, Harvard Medical School, Boston, MA, USA. Electronic address: Kahle.Kristopher@mgh.harvard.edu.

Christopher A WalshDivision of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Howard Hughes Medical Institute, Boston, MA, USA. Electronic address: christopher.walsh@childrens.harvard.edu.

Sattar KhoshkhooDepartment of Neurology, Mass General Brigham, Harvard Medical School, Boston, MA, USA; Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: skhoshkhoo@bwh.harvard.edu.

Funding

Human Epilepsy Genetics Neuronal Migration DisordersR37NS035129 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI Christopher A. Walsh · 2002 to 2026

$6.5M

Genetic and Cellular Mechanisms of Temporal Lobe EpilepsyK08NS128272 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI Sattar Khoshkhoo · 2022 to 2026

$1.2M

NINDS NIH HHS K08 NS128272NINDS NIH HHS R37 NS035129

6 · The paper itself

Abstract

Mesial temporal lobe epilepsy is the most common focal epilepsy in adults and has historically been attributed to acquired hippocampal injury caused by precipitating insults such as prolonged febrile seizures and head trauma. However, recent studies have identified somatic variants activating Ras-MAPK signaling in more than 40% of surgically resected mesial temporal lobe epilepsy (MTLE) hippocampi. These variants, which are enriched in cases with hippocampal sclerosis (MTLE-HS), exhibit evidence of positive clonal selection and are localized to neuroglial lineages arising from hippocampal progenitors. Here, we review emerging evidence supporting a role for somatic Ras-mitogen-activated protein kinase (MAPK) mosaicism in MTLE pathogenesis and propose a two-hit model in which acquired insults promote clonal expansion of Ras-MAPK-mutant progenitors, resulting in aberrant neurogenesis, hippocampal remodeling, and epileptogenesis. These findings suggest new opportunities for disease prevention and precision therapeutics targeting Ras-MAPK signaling.

Identifiers

PMID42762587

DOI10.1016/j.gde.2026.102532

PMCPMC13629604

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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.