Evidence map›Paper›PMID 32705143›Full record

ArticleBrain : a journal of neurology2020

Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants.

Caroline Neuray, Reza Maroofian, Marcello Scala, Tipu Sultan, Gurpur S Pai, Majid Mojarrad, Heba El Khashab, Leigh deHoll, Wyatt Yue, Hessa S Alsaif and 20 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain : a journal of neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.9field-weighted citation impact, top 8% 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

30 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Ventral body wall closure: Mechanistic insights from mouse models and translation to human pathology.Developmental dynamics : an official publication of the American Association of Anatomists · 2025
    Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Allelic heterogeneity and abnormal vesicle recycling inFrontiers in molecular neuroscience · 2024
    Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Review
  19. Review
  20. Article
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

30 authors at 15 institutions in 9 countries.

Caroline NeurayUCL Queen Square Institute of Neurology, University College London, London, UK.
Reza MaroofianUCL Queen Square Institute of Neurology, University College London, London, UK.
Marcello ScalaUCL Queen Square Institute of Neurology, University College London, London, UK.
Tipu SultanDepartment of Pediatric Neurology, Children's Hospital and Institute of Child Health, Lahore, Pakistan.
Gurpur S PaiMedical University of South Carolina, USA.
Majid MojarradDepartment of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Heba El KhashabDepartment of Pediatrics, Children's Hospital, Ain Shams University, Cairo, Egypt.
Leigh deHollMedical University of South Carolina, USA.
Wyatt YueStructural Genomics Consortium, Nuffield Department of Clinical Medicine, University of Oxford, UK.
Hessa S AlsaifStudent Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Maria N ZanettiDepartment of Clinical and Experimental Epilepsy, University College London, London, UK.
Oscar BelloDepartment of Clinical and Experimental Epilepsy, University College London, London, UK.
Richard PersonGeneDx, Gaithersburg, MD, USA.
Atieh EslahiDepartment of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Zaynab KhazaeiGenetic Center of Khorasan Razavi, Mashhad, Iran.
Masoumeh H FeizabadiDepartment of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Stephanie EfthymiouUCL Queen Square Institute of Neurology, University College London, London, UK.
SYNaPS Study Group
Hala T El-BassyouniClinical Genetics Department, National Research Centre, Cairo, Egypt.
Doaa R SolimanDepartment of Pediatrics, Faculty of Medicine, Benha University, Benha, Egypt.
Selahattin TekesDicle University, School of Medicine, Department of Medical Genetics, Diyarbakir, Turkey.
Leyla OzerYuksek Ihtisas University, School of Medicine, Department of Medical Genetics, Ankara, Turkey.
Volkan BaltaciMikrogen Genetic Diagnosis Center, Ankara, Turkey.
Suliman KhanCENTOGENE AG, Rostock.
Christian BeetzCENTOGENE AG, Rostock.
Khalda S AmrMolecular Genetics Department, National Research Centre, Cairo, Egypt.
Vincenzo SalpietroUCL Queen Square Institute of Neurology, University College London, London, UK.
Yalda JamshidiMolecular and Clinical Sciences Institute St George's, University of London, UK.
Fowzan S AlkurayaDepartment of Genetics, King Faisal Specialist Hospital and Research Center Riyadh, Saudi Arabia.
Henry HouldenUCL Queen Square Institute of Neurology, University College London, London, UK.
Medical University of South Carolina · USMashhad University of Medical Sciences · IRNational Hospital for Neurology and Neurosurgery · GBNational Research Centre · EGCentogene (Germany) · DEDicle University · TREpilepsy Research UK · GBSt George's, University of London · GBAin Shams University Hospital · EGBenha University · EGIstituto Giannina Gaslini · ITKing Faisal Specialist Hospital & Research Centre · SAParacelsus Medical University · ATUniversity of Oxford · GBYüksek İhtisas Üniversitesi · TR

Funding

Medical Research Council G0601943Medical Research Council G0802760Medical Research Council G1001253Medical Research Council G108/638Medical Research Council MC_UP_1502/3Medical Research Council MR/J004758/1Medical Research Council MR/S005021/1Medical Research Council MR/S01165X/1The Dunhill Medical Trust R605/0717Wellcome TrustWellcome Trust WT093205Wellcome Trust WT104033AIA
6 · The paper itself

Abstract

Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to ∼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1-/- mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy.

Indexed as

Abnormalities, MultipleAge of OnsetAllelesChildChild, PreschoolEpilepsyFemaleGlutamate DecarboxylaseHumansInfantMaleMuscle HypotoniaMutationNeurodevelopmental DisordersGlutamate Decarboxylaseglutamate decarboxylase 1cleft palateepilepsyGAD1muscle weaknessneurodevelopmental delay

Identifiers

PMID32705143
PMCPMC7447512
OpenAlexW3044972848

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.