Evidence map›Paper›PMID 33055295›Full record

ArticleEuropean journal of endocrinology2020

Rare CNVs provide novel insights into the molecular basis of GH and IGF-1 insensitivity.

Emily Cottrell, Claudia P Cabrera, Miho Ishida, Sumana Chatterjee, James Greening, Neil Wright, Artur Bossowski, Leo Dunkel, Asma Deeb, Iman Al Basiri and 8 more

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

Article in European journal of endocrinology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 22% 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

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. 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

18 authors at 13 institutions in 5 countries.

Emily CottrellCentre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
Claudia P CabreraCentre for Translational Bioinformatics, Queen Mary University of London, London, UK.
Miho IshidaUniversity College London, Great Ormond Street Institute of Child Health, London, UK.
Sumana ChatterjeeCentre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
James GreeningUniversity Hospitals of Leicester NHS Trust, Leicester, UK.
Neil WrightThe University of Sheffield Faculty of Medicine, Dentistry and Health, Sheffield, UK.
Artur BossowskiDepartment of Pediatrics, Endocrinology and Diabetes with a Cardiology Unit, Medical University of Bialystok, Bialystok, Poland.
Leo DunkelCentre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
Asma DeebPaediatric Endocrinology Department, Mafraq Hospital, Abu Dhabi, United Arab Emirates.
Iman Al BasiriMubarak Al-kabeer Hospital, Jabriya, Kuwait.
Stephen J RoseUniversity Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Avril MasonRoyal Hospital for Children, Glasgow, UK.
Susan BintViapath, Guy's Hospital, London, UK.
Joo Wook AhnAddenbrookes Hospital, Cambridge, UK.
Vivian HwaCincinnati Center for Growth Disorders, Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Louise A MetherellCentre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
Gudrun E MooreUniversity College London, Great Ormond Street Institute of Child Health, London, UK.
Helen L StorrCentre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
William Harvey Research Institute · GBGreat Ormond Street Hospital · GBAddenbrooke's Hospital · GBGuy's Hospital · GBMafraq Hospital · AEMedical University of Białystok · PLMubarak Al Kabeer Hospital · KWQueen Mary University of London · GBRoyal Hospital for Children · GBUniversity Hospitals Birmingham NHS Foundation Trust · GBUniversity Hospitals of Leicester NHS Trust · GBUniversity of Cincinnati · USUniversity of Sheffield · GB

Funding

Pluripotent Stem Cell-derived Liver Organoids as a Patient-based New Model for Deliverable Assessment of GH Insensitivity SyndromeR21HD098417 · NICHD · CINCINNATI CHILDRENS HOSP MED CTR · PI HWA, VIVIAN · 2019 to 2020
$437k
Department of Health NIHR300098NICHD NIH HHS R21 HD098417
6 · The paper itself

Abstract

objectiveCopy number variation (CNV) has been associated with idiopathic short stature, small for gestational age and Silver-Russell syndrome (SRS). It has not been extensively investigated in growth hormone insensitivity (GHI; short stature, IGF-1 deficiency and normal/high GH) or previously in IGF-1 insensitivity (short stature, high/normal GH and IGF-1). DESIGN AND

methodsArray comparative genomic hybridisation was performed with ~60 000 probe oligonucleotide array in GHI (n = 53) and IGF-1 insensitivity (n = 10) subjects. Published literature, mouse models, DECIPHER CNV tracks, growth associated GWAS loci and pathway enrichment analyses were used to identify key biological pathways/novel candidate growth genes within the CNV regions.

resultsBoth cohorts were enriched for class 3-5 CNVs (7/53 (13%) GHI and 3/10 (30%) IGF-1 insensitivity patients). Interestingly, 6/10 (60%) CNV subjects had diagnostic/associated clinical features of SRS. 5/10 subjects (50%) had CNVs previously reported in suspected SRS: 1q21 (n = 2), 12q14 (n = 1) deletions and Xp22 (n = 1), Xq26 (n = 1) duplications. A novel 15q11 deletion, previously associated with growth failure but not SRS/GHI was identified. Bioinformatic analysis identified 45 novel candidate growth genes, 15 being associated with growth in GWAS. The WNT canonical pathway was enriched in the GHI cohort and CLOCK was identified as an upstream regulator in the IGF-1 insensitivity cohorts.

conclusionsOur cohort was enriched for low frequency CNVs. Our study emphasises the importance of CNV testing in GHI and IGF-1 insensitivity patients, particularly GHI subjects with SRS features. Functional experimental evidence is now required to validate the novel candidate growth genes, interactions and biological pathways identified.

Indexed as

AdolescentChildChild, PreschoolCohort StudiesDNA Copy Number VariationsFemaleGenetic TestingHuman Growth HormoneHumansInfantInsulin-Like Growth Factor IMaleHuman Growth HormoneIGF1 protein, humanInsulin-Like Growth Factor I

Identifiers

PMID33055295
PMCPMC7592635
OpenAlexW3093218374

What Socratic holds

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LicenceCC BY
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Registered trials

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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.