Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 518

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

Brain somatic mutations in MTOR cause focal cortical dysplasia type II leading to intractable epilepsy

Open access
Lim, Jae Seok, Kim, Woo-il, Kang, Hoon-Chul, Kim, Se Hoon, Park, Ah Hyung, Park, Eun Kyung, Cho, Young-Wook, Kim, Sangwoo, Kim, Ho Min, Kim, Jeong A, Kim, Junho, Rhee, Hwanseok, Kang, Seok-Gu, Kim, Heung Dong, Kim, Daesoo, Kim, Dong-Seok, Lee, Jeong Ho·2015·Nature Medicine
DOI 10.1038/nm.3824
Open this paper in CoChat — free account

Abstract

Focal cortical dysplasia type II (FCDII) is a sporadic developmental malformation of the cerebral cortex characterized by dysmorphic neurons, dyslamination and medically refractory epilepsy. It has been hypothesized that FCD is caused by somatic mutations in affected regions. Here, we used deep whole-exome sequencing (read depth, 412–668×) validated by site-specific amplicon sequencing (100–347,499×) in paired brain-blood DNA from four subjects with FCDII and uncovered a de novo brain somatic mutation, mechanistic target of rapamycin (MTOR) c.7280T>C (p.Leu2427Pro) in two subjects. Deep sequencing of the MTOR gene in an additional 73 subjects with FCDII using hybrid capture and PCR amplicon sequencing identified eight different somatic missense mutations found in multiple brain tissue samples of ten subjects. The identified mutations accounted for 15.6% of all subjects with FCDII studied (12 of 77). The identified mutations induced the hyperactivation of mTOR kinase. Focal cortical expression of mutant MTOR by in utero electroporation in mice was sufficient to disrupt neuronal migration and cause spontaneous seizures and cytomegalic neurons. Inhibition of mTOR with rapamycin suppressed cytomegalic neurons and epileptic seizures. This study provides, to our knowledge, the first evidence that brain somatic activating mutations in MTOR cause FCD and identifies mTOR as a treatment target for intractable epilepsy in FCD.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/nm.3824

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 3 references

Cited by

Metadata

Authors
Lim, J. S., Kim, W.-I., Kang, H.-C., Kim, S. H., Park, A. H., Park, E. K., Cho, Y.-W., Kim, S., Kim, H. M., Kim, J. A., Kim, J., Rhee, H., Kang, S.-G., Kim, H. D., Kim, D., Kim, D.-S., & Lee, J. H.
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2015-03-23
Volume
21
Issue
4
Pages
395-400
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/nm.3824
OpenAlex
W1987182404
Cited by
518
References
3
FWCI
36.42
Type
journal article
Language
en
Open access
green

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.