Evidence map›Paper›PMID 27137492›Full record

ArticleEMBO molecular medicine2016

IGSF10 mutations dysregulate gonadotropin-releasing hormone neuronal migration resulting in delayed puberty.

Sasha R Howard, Leonardo Guasti, Gerard Ruiz-Babot, Alessandra Mancini, Alessia David, Helen L Storr, Lousie A Metherell, Michael Je Sternberg, Claudia P Cabrera, Helen R Warren and 10 more

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

Article in EMBO molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 1 pooled it
17.2field-weighted citation impact, top 1% 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

69 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Genetics of Idiopathic Hypogonadotropic HypogonadismJournal of clinical research in pediatric endocrinology · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Disorders of puberty and neurodevelopment: A shared etiology?Annals of the New York Academy of Sciences · 2024
    Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Genetics of pubertal delay.Clinical endocrinology · 2022
    Review

9 more citing papers are in PubMed but not listed here.

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

20 authors at 7 institutions in 5 countries.

Sasha R HowardCentre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Leonardo GuastiCentre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Gerard Ruiz-BabotCentre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Alessandra ManciniCentre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Alessia DavidCentre for Integrative Systems Biology and Bioinformatics, Department of Life Sciences, Imperial College London, London, UK.
Helen L StorrCentre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Lousie A MetherellCentre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Michael Je SternbergCentre for Integrative Systems Biology and Bioinformatics, Department of Life Sciences, Imperial College London, London, UK.
Claudia P CabreraCentre for Translational Bioinformatics, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK.
Helen R WarrenNIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK Department of Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London, UK.
Michael R BarnesCentre for Translational Bioinformatics, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK.
Richard QuintonInstitute of Genetic Medicine University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, UK.
Nicolas de RouxUnité Mixte de Recherche 1141, Institut National de la Santé et de la Recherche Médicale, Paris, France Université Paris Diderot, Sorbonne Paris Cité, Hôpital Robert Debré, Paris, France Laboratoire de Biochimie, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Paris, France.
Jacques YoungUniv Paris-Sud, Le Kremlin Bicêtre, France INSERM UMR-1185, Le Kremlin Bicêtre, France Assistance Publique-Hôpitaux de Paris, Bicêtre Hospital, Le Kremlin-Bicêtre, France Department of Reproductive Endocrinology, Bicêtre Hospital, Le Kremlin-Bicêtre, France.
Anne Guiochon-MantelUniv Paris-Sud, Le Kremlin Bicêtre, France INSERM UMR-1185, Le Kremlin Bicêtre, France Assistance Publique-Hôpitaux de Paris, Bicêtre Hospital, Le Kremlin-Bicêtre, France.
Karoliina WehkalampiChildren's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Valentina AndréDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy.
Yoav GothilfDepartment of Neurobiology, The George S. Wise Faculty of Life Sciences and Sagol School of Neuroscience, Tel-Aviv University, Tel Aviv, Israel.
Anna CariboniDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy Institute of Ophthalmology, University College London (UCL), London, UK.
Leo DunkelCentre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK l.dunkel@qmul.ac.uk.ORCID 0000-0003-4008-8521
Queen Mary University of London · GBInserm · FRImperial College London · GBUniversity of Milan · ITNewcastle University · GBTel Aviv University · ILUniversity of Helsinki · FI

Funding

Biotechnology and Biological Sciences Research Council BB/L002671/1Medical Research Council MR/K006584/1Medical Research Council MR/K020455/1Medical Research Council MR/K021613/1Wellcome TrustWellcome Trust 102745
6 · The paper itself

Abstract

Early or late pubertal onset affects up to 5% of adolescents and is associated with adverse health and psychosocial outcomes. Self-limited delayed puberty (DP) segregates predominantly in an autosomal dominant pattern, but the underlying genetic background is unknown. Using exome and candidate gene sequencing, we have identified rare mutations in IGSF10 in 6 unrelated families, which resulted in intracellular retention with failure in the secretion of mutant proteins. IGSF10 mRNA was strongly expressed in embryonic nasal mesenchyme, during gonadotropin-releasing hormone (GnRH) neuronal migration to the hypothalamus. IGSF10 knockdown caused a reduced migration of immature GnRH neurons in vitro, and perturbed migration and extension of GnRH neurons in a gnrh3:EGFP zebrafish model. Additionally, loss-of-function mutations in IGSF10 were identified in hypothalamic amenorrhea patients. Our evidence strongly suggests that mutations in IGSF10 cause DP in humans, and points to a common genetic basis for conditions of functional hypogonadotropic hypogonadism (HH). While dysregulation of GnRH neuronal migration is known to cause permanent HH, this is the first time that this has been demonstrated as a causal mechanism in DP‡.

Indexed as

Cell MovementAdolescentAnimalsDNA Mutational AnalysisFemaleGonadotropin-Releasing HormoneHumansHypothalamusImmunoglobulinsMaleModels, AnimalMutant ProteinsNeuronsPuberty, DelayedSequence Analysis, DNAZebrafishGonadotropin-Releasing HormoneIGSF10 protein, humanImmunoglobulinsMutant Proteinsdelayed pubertyGnRHhypothalamic amenorrheaneuronal migrationpuberty

Identifiers

PMID27137492
PMCPMC4888853
OpenAlexW2336236331

What OpenQuestion holds

Textmetadata
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.