Evidence map›Paper›PMID 38496361›Full record

ArticleNeurology. Genetics2024

Ectopic HCN4 Provides a Target Biomarker for the Genetic Spectrum of mTORopathies.

Matthew Coleman, Paulo Pinares-Garcia, Sarah E Stephenson, Wei Shern Lee, Daniz Kooshavar, Catriona A Mclean, Katherine B Howell, Richard J Leventer, Christopher A Reid, Paul J Lockhart

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PubMed Full text at PMC Publisher
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Article in Neurology. Genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.0field-weighted citation impact, top 26% of its field
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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

Who cites it

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
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4 · The record

Corrections and comments

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

10 authors at 1 institution in 1 country.

Matthew ColemanFrom the Murdoch Children's Research Institute (M.C., S.E.S., W.S.L., D.K., K.B.H., R.J.L., P.J.L.); Department of Paediatrics (M.C., S.E.S., D.K., K.B.H., R.J.L., P.J.L.), University of Melbourne; The Florey Institute of Neuroscience and Mental Health (P.P.-G., C.A.R.), Parkville; Alfred Hospital (C.A.M.), Prahran; Department of Neurology (K.B.H., R.J.L.), The Royal Children's Hospital, Parkville; and Epilepsy Research Centre (C.A.R.), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victory, Australia.
Paulo Pinares-GarciaFrom the Murdoch Children's Research Institute (M.C., S.E.S., W.S.L., D.K., K.B.H., R.J.L., P.J.L.); Department of Paediatrics (M.C., S.E.S., D.K., K.B.H., R.J.L., P.J.L.), University of Melbourne; The Florey Institute of Neuroscience and Mental Health (P.P.-G., C.A.R.), Parkville; Alfred Hospital (C.A.M.), Prahran; Department of Neurology (K.B.H., R.J.L.), The Royal Children's Hospital, Parkville; and Epilepsy Research Centre (C.A.R.), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victory, Australia.
Sarah E StephensonFrom the Murdoch Children's Research Institute (M.C., S.E.S., W.S.L., D.K., K.B.H., R.J.L., P.J.L.); Department of Paediatrics (M.C., S.E.S., D.K., K.B.H., R.J.L., P.J.L.), University of Melbourne; The Florey Institute of Neuroscience and Mental Health (P.P.-G., C.A.R.), Parkville; Alfred Hospital (C.A.M.), Prahran; Department of Neurology (K.B.H., R.J.L.), The Royal Children's Hospital, Parkville; and Epilepsy Research Centre (C.A.R.), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victory, Australia.
Wei Shern LeeFrom the Murdoch Children's Research Institute (M.C., S.E.S., W.S.L., D.K., K.B.H., R.J.L., P.J.L.); Department of Paediatrics (M.C., S.E.S., D.K., K.B.H., R.J.L., P.J.L.), University of Melbourne; The Florey Institute of Neuroscience and Mental Health (P.P.-G., C.A.R.), Parkville; Alfred Hospital (C.A.M.), Prahran; Department of Neurology (K.B.H., R.J.L.), The Royal Children's Hospital, Parkville; and Epilepsy Research Centre (C.A.R.), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victory, Australia.
Daniz KooshavarFrom the Murdoch Children's Research Institute (M.C., S.E.S., W.S.L., D.K., K.B.H., R.J.L., P.J.L.); Department of Paediatrics (M.C., S.E.S., D.K., K.B.H., R.J.L., P.J.L.), University of Melbourne; The Florey Institute of Neuroscience and Mental Health (P.P.-G., C.A.R.), Parkville; Alfred Hospital (C.A.M.), Prahran; Department of Neurology (K.B.H., R.J.L.), The Royal Children's Hospital, Parkville; and Epilepsy Research Centre (C.A.R.), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victory, Australia.
Catriona A McleanFrom the Murdoch Children's Research Institute (M.C., S.E.S., W.S.L., D.K., K.B.H., R.J.L., P.J.L.); Department of Paediatrics (M.C., S.E.S., D.K., K.B.H., R.J.L., P.J.L.), University of Melbourne; The Florey Institute of Neuroscience and Mental Health (P.P.-G., C.A.R.), Parkville; Alfred Hospital (C.A.M.), Prahran; Department of Neurology (K.B.H., R.J.L.), The Royal Children's Hospital, Parkville; and Epilepsy Research Centre (C.A.R.), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victory, Australia.ORCID https://orcid.org/0000-0002-0302-5727
Katherine B HowellFrom the Murdoch Children's Research Institute (M.C., S.E.S., W.S.L., D.K., K.B.H., R.J.L., P.J.L.); Department of Paediatrics (M.C., S.E.S., D.K., K.B.H., R.J.L., P.J.L.), University of Melbourne; The Florey Institute of Neuroscience and Mental Health (P.P.-G., C.A.R.), Parkville; Alfred Hospital (C.A.M.), Prahran; Department of Neurology (K.B.H., R.J.L.), The Royal Children's Hospital, Parkville; and Epilepsy Research Centre (C.A.R.), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victory, Australia.
Richard J LeventerFrom the Murdoch Children's Research Institute (M.C., S.E.S., W.S.L., D.K., K.B.H., R.J.L., P.J.L.); Department of Paediatrics (M.C., S.E.S., D.K., K.B.H., R.J.L., P.J.L.), University of Melbourne; The Florey Institute of Neuroscience and Mental Health (P.P.-G., C.A.R.), Parkville; Alfred Hospital (C.A.M.), Prahran; Department of Neurology (K.B.H., R.J.L.), The Royal Children's Hospital, Parkville; and Epilepsy Research Centre (C.A.R.), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victory, Australia.
Christopher A ReidFrom the Murdoch Children's Research Institute (M.C., S.E.S., W.S.L., D.K., K.B.H., R.J.L., P.J.L.); Department of Paediatrics (M.C., S.E.S., D.K., K.B.H., R.J.L., P.J.L.), University of Melbourne; The Florey Institute of Neuroscience and Mental Health (P.P.-G., C.A.R.), Parkville; Alfred Hospital (C.A.M.), Prahran; Department of Neurology (K.B.H., R.J.L.), The Royal Children's Hospital, Parkville; and Epilepsy Research Centre (C.A.R.), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victory, Australia.
Paul J LockhartFrom the Murdoch Children's Research Institute (M.C., S.E.S., W.S.L., D.K., K.B.H., R.J.L., P.J.L.); Department of Paediatrics (M.C., S.E.S., D.K., K.B.H., R.J.L., P.J.L.), University of Melbourne; The Florey Institute of Neuroscience and Mental Health (P.P.-G., C.A.R.), Parkville; Alfred Hospital (C.A.M.), Prahran; Department of Neurology (K.B.H., R.J.L.), The Royal Children's Hospital, Parkville; and Epilepsy Research Centre (C.A.R.), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victory, Australia.ORCID https://orcid.org/0000-0003-2531-8413
Norwegian Womens Public Health Association · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background and Objectives: Pathogenic variants in PI3K-AKT-mTOR pathway and GATOR1 complex genes resulting in hyperactivation of mechanistic target of rapamycin (mTOR) complex 1 are a major cause of drug-resistant epilepsy and focal cortical malformations (FCM). Resective neurosurgery is often required to achieve seizure control in patients with mTORopathies due to lack of effectiveness of nonsurgical therapies, including antiseizure medication and mTOR inhibitors. Elevated hyperpolarization-activated cyclic nucleotide-gated potassium channel isoform 4 (HCN4) has been proposed as a key marker in some mTOR-related brain malformations. This study aimed to investigate HCN4 as a biomarker in the brain across the genetic spectrum of mTORopathies in humans. Methods: Our study investigated the relative steady-state levels and cellular localization of HCN4 in resected human brain tissue from 18 individuals with mTORopathies (3 individuals with tuberous sclerosis complex (TSC) due to Results: Elevated HCN4 was observed to be highly restricted to abnormal cell types (dysmorphic neurons and balloon cells) in brain tissue from all mTORopathy tissues ( Discussion: HCN4 provides a biomarker for the genetic spectrum of mTORopathies and may present a potential therapeutic target for seizure control in mTOR-related epilepsy.

Identifiers

PMID38496361
PMCPMC10940058
OpenAlexW4392691633

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