Evidence map›Paper›PMID 36810932›Full record

ArticleDisease models & mechanisms2023

Autism-linked NLGN3 is a key regulator of gonadotropin-releasing hormone deficiency.

Roberto Oleari, Antonella Lettieri, Stefano Manzini, Alyssa Paganoni, Valentina André, Paolo Grazioli, Marco Busnelli, Paolo Duminuco, Antonio Vitobello, Christophe Philippe and 9 more

Open access · goldAbstract read
In one paragraph

Article in Disease models & mechanisms, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.0field-weighted citation impact, top 15% 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

8 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Disorders of puberty and neurodevelopment: A shared etiology?Annals of the New York Academy of Sciences · 2024
    Review
  5. Review
  6. Article
  7. Article
  8. 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

19 authors at 6 institutions in 4 countries.

Roberto OleariDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Milan 20133, Italy.ORCID 0000-0002-5692-3328
Antonella LettieriCRC Aldo Ravelli for Neurotechnology and Experimental Brain Therapeutics, Department of Health Sciences, University of Milan, Milan 20142, Italy.ORCID 0000-0001-7750-0423
Stefano ManziniDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Milan 20133, Italy.ORCID 0000-0002-1232-2635
Alyssa PaganoniDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Milan 20133, Italy.ORCID 0000-0001-9393-9356
Valentina AndréDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Milan 20133, Italy.
Paolo GrazioliDepartment of Health Sciences, University of Milan, Milan 20142, Italy.ORCID 0000-0001-9120-4217
Marco BusnelliDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Milan 20133, Italy.
Paolo DuminucoLaboratory of Endocrine and Metabolic Research, IRCCS Istituto Auxologico Italiano, Cusano Milanino 20095, Italy.
Antonio VitobelloUnité Fonctionnelle Innovation en Diagnostic Génomique des Maladies Rares, Fédération Hospitalo-Universitaire (FHU) TRANSLAD, CHU Dijon Bourgogne, Dijon 21079, France.
Christophe PhilippeUnité Fonctionnelle Innovation en Diagnostic Génomique des Maladies Rares, Fédération Hospitalo-Universitaire (FHU) TRANSLAD, CHU Dijon Bourgogne, Dijon 21079, France.
Varoona BizaouiGenetics and Neurodevelopment, Centre Hospitalier de l'Estran, Pontorson 50170, France.ORCID 0000-0001-6335-7419
Helen L StorrCentre for Endocrinology William Harvey Research Institute Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
Federica AmorusoDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Milan 20133, Italy.ORCID 0000-0002-6832-6053
Fani MemiWellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge CB2 0AW, UK.
Valeria VezzoliLaboratory of Endocrine and Metabolic Research, IRCCS Istituto Auxologico Italiano, Cusano Milanino 20095, Italy.
Valentina MassaCRC Aldo Ravelli for Neurotechnology and Experimental Brain Therapeutics, Department of Health Sciences, University of Milan, Milan 20142, Italy.ORCID 0000-0003-2246-9515
Peter ScheiffeleBiozentrum of the University of Basel, Basel 4056, Switzerland.ORCID 0000-0002-9516-9399
Sasha R HowardCentre for Endocrinology William Harvey Research Institute Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.ORCID 0000-0002-6698-903X
Anna CariboniDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Milan 20133, Italy.ORCID 0000-0001-8630-8361
University of Milan · ITInserm · FRIRCCS Istituto Auxologico Italiano · ITQueen Mary University of London · GBUniversity of Basel · CHWellcome/MRC Cambridge Stem Cell Institute · GB

Funding

Barts Charity MGU0552British Society for NeuroendocrinologyCollegio Ghislieri di PaviaEuropean Society for Paediatric EndocrinologyInnovative Medicines Initiative 777394Ministero della Salute GR-2016-02362389National Institute for Health and Care Research CL-2017-19-002Rosetrees Trust M222-F1Wellcome TrustWellcome Trust 222049/Z/20/Z
6 · The paper itself

Abstract

Gonadotropin-releasing hormone (GnRH) deficiency (GD) is a disorder characterized by absent or delayed puberty, with largely unknown genetic causes. The purpose of this study was to obtain and exploit gene expression profiles of GnRH neurons during development to unveil novel biological mechanisms and genetic determinants underlying GD. Here, we combined bioinformatic analyses of immortalized and primary embryonic GnRH neuron transcriptomes with exome sequencing from GD patients to identify candidate genes implicated in the pathogenesis of GD. Among differentially expressed and filtered transcripts, we found loss-of-function (LoF) variants of the autism-linked neuroligin 3 (NLGN3) gene in two unrelated patients co-presenting with GD and neurodevelopmental traits. We demonstrated that NLGN3 is upregulated in maturing GnRH neurons and that NLGN3 wild-type, but not mutant, protein promotes neuritogenesis when overexpressed in developing GnRH cells. Our data represent proof of principle that this complementary approach can identify new candidate GD genes and demonstrate that LoF NLGN3 variants can contribute to GD. This novel genotype-phenotype correlation implies common genetic mechanisms underlying neurodevelopmental disorders, such as GD and autistic spectrum disorder.

Indexed as

Autistic DisorderCell Adhesion Molecules, NeuronalGonadotropin-Releasing HormoneHumansMembrane ProteinsNerve Tissue ProteinsCell Adhesion Molecules, NeuronalGonadotropin-Releasing HormoneMembrane ProteinsNerve Tissue Proteinsneuroligin 3Autism spectrum disorderDelayed pubertyGnRH neuronsNeuritogenesisNLGN3Transcriptome

Identifiers

PMID36810932
PMCPMC10110398
OpenAlexW4321496989

What Socratic 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 Socratic graph.