Evidence map›Paper›PMID 30982611›Full record

ArticleAmerican journal of human genetics2019

Pathogenic Variants in GPC4 Cause Keipert Syndrome.

David J Amor, Sarah E M Stephenson, Mirna Mustapha, Martin A Mensah, Charlotte W Ockeloen, Wei Shern Lee, Rick M Tankard, Dean G Phelan, Marwan Shinawi, Arjan P M de Brouwer and 20 more

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

Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

16 citing papers in PubMed, 31 citations in OpenAlex.

  1. A Combination of Variants in SEPTIN9 and MSX1 Genes Leads to the Formation of Orofacial Clefts.Genes to cells : devoted to molecular & cellular mechanisms · 2026
    Article
  2. Keipert syndrome beyond classical features: novel GPC4 variant associated with epilepsy but preserved cognition.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Article
  3. Article
  4. Review
  5. Macrocephaly and Finger Changes: A Narrative Review.International journal of molecular sciences · 2024
    Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Coreceptor functions of cell surface heparan sulfate proteoglycans.American journal of physiology. Cell physiology · 2022
    Review
  11. The function of glypicans in the mammalian embryo.American journal of physiology. Cell physiology · 2022
    Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
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 18 institutions in 9 countries.

David J AmorMurdoch Children's Research Institute, Flemington Road, Parkville, Victoria 3052, Australia; Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia.
Sarah E M StephensonMurdoch Children's Research Institute, Flemington Road, Parkville, Victoria 3052, Australia; Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia.
Mirna MustaphaDepartment of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, CA 94305, USA.
Martin A MensahInstitut für Medizinische Genetik, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin 13353, Germany.
Charlotte W OckeloenDepartment of Human Genetics, Radboud University Medical Center, Nijmegen 6500 HB, the Netherlands.
Wei Shern LeeMurdoch Children's Research Institute, Flemington Road, Parkville, Victoria 3052, Australia; Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia.
Rick M TankardThe Walter and Eliza Hall Institute of Medical Research, Royal Parade, Parkville, Victoria 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
Dean G PhelanMurdoch Children's Research Institute, Flemington Road, Parkville, Victoria 3052, Australia; Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia.
Marwan ShinawiDepartment of Pediatrics, Division of Genetics and Genomic Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Arjan P M de BrouwerDepartment of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6500HB Nijmegen, The Netherlands.
Rolph PfundtDepartment of Human Genetics, Radboud University Medical Center, Nijmegen 6500 HB, the Netherlands.
Cari DowlingMolecular Neurobiology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Tomi L TolerDepartment of Pediatrics, Division of Genetics and Genomic Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
V Reid SuttonDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA.
Emanuele AgoliniLaboratory of Medical Genetics, Department of Laboratories, IRCCS Bambino Gesù Children's Hospital, Rome 00165, Italy.
Martina RinelliLaboratory of Medical Genetics, Department of Laboratories, IRCCS Bambino Gesù Children's Hospital, Rome 00165, Italy.
Rossella CapolinoMedical Genetics, Department of Pediatrics, IRCCS Bambino Gesù Children's Hospital, Rome 00165, Italy.
Diego MartinelliDivision of Metabolism, Department of Pediatric Subspecialties, IRCCS Bambino Gesù Children's Hospital Rome 00165, Italy.
Giuseppe ZampinoCenter for Rare Disease and Congenital Defects, Fondazione Policlinico Universitario A. Gemelli, Catholic University, Rome 00168, Italy.
Miroslav DumićDepartment of Pediatrics Rebro, University of Zagreb Medical School, Kispaticeva 12, 10 000 Zagreb, Croatia.
William ReardonDepartment of Clinical Genetics, Our Lady's Children Hospital Crumlin, Dublin, D12, V004, Ireland.
Charles Shaw-SmithDepartment of Clinical Genetics, Royal Devon and Exeter National Health Service Foundation Trust, Exeter EX1 2ED, UK.
Richard J LeventerMurdoch Children's Research Institute, Flemington Road, Parkville, Victoria 3052, Australia; Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia; Department of Neurology, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia.
Martin B DelatyckiMurdoch Children's Research Institute, Flemington Road, Parkville, Victoria 3052, Australia; Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia.
Tjitske KleefstraDepartment of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6500HB Nijmegen, The Netherlands.
Stefan MundlosInstitut für Medizinische Genetik, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin 13353, Germany.
Geert MortierDepartment of Medical Genetics, Antwerp University Hospital and University of Antwerp, B-2650 Antwerp (Edegem), Belgium.
Melanie BahloThe Walter and Eliza Hall Institute of Medical Research, Royal Parade, Parkville, Victoria 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
Nicola J AllenMolecular Neurobiology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Paul J LockhartMurdoch Children's Research Institute, Flemington Road, Parkville, Victoria 3052, Australia; Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia. Electronic address: paul.lockhart@mcri.edu.au.
University of Melbourne · AURadboud University Medical Center · NLBambino Gesù Children's Hospital · ITCharité - Universitätsmedizin Berlin · DEIstituti di Ricovero e Cura a Carattere Scientifico · ITRoyal Children's Hospital · AUSalk Institute for Biological Studies · USWalter and Eliza Hall Institute of Medical Research · AUWashington University in St. Louis · USAgostino Gemelli University Polyclinic · ITAntwerp University Hospital · BEMurdoch Children's Research Institute · AUNational Health Service · GBOur Lady's Hospital · IERadboud University Nijmegen · NLStanford University · USTexas Children's Hospital · USUniversity of Zagreb · HR

Funding

Baylor-Johns Hopkins Center for Mendelian GeneticsUM1HG006542 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2016 to 2020
$14.5M
Astrocyte regulation of neuronal AMPA glutamate receptorsR01NS089791 · NINDS · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI ALLEN, NICOLA J · 2014 to 2023
$4.2M
Understanding thyroid hormone regulation of neurogenesis in the cochleaR01DC009590 · NIDCD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MUSTAPHA, MIRNA · 2009 to 2013
$1.8M
NHGRI NIH HHS UM1 HG006542NIDCD NIH HHS R01 DC009590NINDS NIH HHS R01 NS089791
6 · The paper itself

Abstract

Glypicans are a family of cell-surface heparan sulfate proteoglycans that regulate growth-factor signaling during development and are thought to play a role in the regulation of morphogenesis. Whole-exome sequencing of the Australian family that defined Keipert syndrome (nasodigitoacoustic syndrome) identified a hemizygous truncating variant in the gene encoding glypican 4 (GPC4). This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites. We subsequently identified seven affected males from five additional kindreds with novel and predicted pathogenic variants in GPC4. Segregation analysis and X-inactivation studies in carrier females provided supportive evidence that the GPC4 variants caused the condition. Furthermore, functional studies of recombinant protein suggested that the truncated proteins p.Gln506

Indexed as

Genetic VariationAdultChildChild, PreschoolDeafnessFemaleGenetic Diseases, X-LinkedGlypicansHumansInfantLower Extremity Deformities, CongenitalMalePedigreePhenotypeYoung AdultGlypicansGPC4 protein, humanglypicansGPC4Keipert syndromeNasodigitoacoustic syndrome

Identifiers

PMID30982611
PMCPMC6507040
OpenAlexW2936272795

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.