Evidence map›Paper›PMID 30290151›Full record

ArticleAmerican journal of human genetics2018

A Recurrent De Novo Heterozygous COG4 Substitution Leads to Saul-Wilson Syndrome, Disrupted Vesicular Trafficking, and Altered Proteoglycan Glycosylation.

Carlos R Ferreira, Zhi-Jie Xia, Aurélie Clément, David A Parry, Mariska Davids, Fulya Taylan, Prashant Sharma, Coleman T Turgeon, Bernardo Blanco-Sánchez, Bobby G Ng and 46 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of human genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02450851 (Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network), which is not on this map. Cited by 49 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 1 pooled it
7.8field-weighted citation impact, top 2% 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.

NCT02450851 recruitingnot on this map

Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network

TypeobservationalSponsorNational Human Genome Research Institute (NHGRI)Ran2015 to 2028Enrolled20,000ConditionsGenetic Disease
3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.

  1. Pooled it
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  17. CDG or not CDG.Journal of inherited metabolic disease · 2022
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

56 authors at 20 institutions in 8 countries.

Carlos R FerreiraMedical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA; Division of Genetics and Metabolism, Children's National Health System, Washington, DC 20010, USA. Electronic address: carlos.ferreira@nih.gov.
Zhi-Jie XiaHuman Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Aurélie ClémentInstitute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.
David A ParryMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Mariska DavidsOffice of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Fulya TaylanDepartment of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, 17176 Stockholm, Sweden.
Prashant SharmaOffice of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Coleman T TurgeonBiochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Bernardo Blanco-SánchezInstitute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.
Bobby G NgHuman Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Clare V LoganMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Lynne A WolfeOffice of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Benjamin D SolomonGeneDx, Gaithersburg, MD 20877, USA.
Megan T ChoGeneDx, Gaithersburg, MD 20877, USA.
Ganka DouglasGeneDx, Gaithersburg, MD 20877, USA.
Daniel R CarvalhoGenetic Unit, SARAH Network of Rehabilitation Hospitals, Brasília-DF, 70335-901, Brazil.
Heiko BratkeDepartment of Internal Medicine, Section of Paediatrics, Haugesund District Hospital, Fonna Health Trust, 5527 Haugesund, Norway.
Marte Gjøl HaugDepartment of Medical Genetics, St. Olav's Hospital, 7006 Trondheim, Norway.
Jennifer B PhillipsInstitute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.
Jeremy WegnerInstitute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.
Michael TiemeyerComplex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.
Kazuhiro AokiComplex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.
Undiagnosed Diseases Network
Scottish Genome Partnership
Ann NordgrenDepartment of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, 17176 Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, 17176 Stockholm, Sweden.
Anna HammarsjöDepartment of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, 17176 Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, 17176 Stockholm, Sweden.
Angela L DukerDivision of Orthogenetics, A.I. duPont Hospital for Children, Wilmington, DE, 19803, USA.
Luis RohenaDivision of Genetics, Department of Pediatrics, San Antonio Military Medical Center, San Antonio, TX, 78234, USA; Department of Pediatrics, University of Texas Health Science Center, San Antonio, TX, 78229, USA.
Hanne Buciek HoveSection of Rare Disorders, Department of Pediatrics, Rigshospitalet, 2100 Copenhagen, Denmark.
Jakob EkDepartment of Clinical Genetics, Rigshospitalet, 2100 Copenhagen, Denmark.
David AdamsOffice of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cynthia J TifftOffice of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Tito OnyekweliOffice of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Tara WeixelOffice of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Ellen MacnamaraOffice of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Kelly RadtkeAmbry Genetics, Aliso Viejo, CA 92656, USA.
Zöe PowisAmbry Genetics, Aliso Viejo, CA 92656, USA.
Dawn EarlDivision of Genetic Medicine, Seattle Children's, Seattle, WA, 98105, USA.
Melissa GabrielDivision of Medical Genetics, Children's Hospital of Los Angeles, University of Southern California, Los Angeles, CA 90027, USA.
Alvaro H Serrano RussiDivision of Medical Genetics, Children's Hospital of Los Angeles, University of Southern California, Los Angeles, CA 90027, USA.
Lauren BrickDivision of Genetics, Department of Pediatrics, McMaster Children's Hospital, McMaster University, Hamilton Ontario L8S 4J9, Canada.
Mariya KozenkoDivision of Genetics, Department of Pediatrics, McMaster Children's Hospital, McMaster University, Hamilton Ontario L8S 4J9, Canada.
Emma ThamDepartment of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, 17176 Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, 17176 Stockholm, Sweden.
Kimiyo M RaymondBiochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
John A PhillipsDivision of Medical genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
George E TillerDepartment of Genetics, Kaiser Permanente, Los Angeles, CA 90027, USA.
William G WilsonDepartment of Pediatrics, University of Virginia Health System, Charlottesville, VA 20903, USA.
Rizwan HamidDivision of Medical genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
May C V MalicdanOffice of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Gen NishimuraLaboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo 108-8639, Japan; Center for Intractable Diseases, Saitama Medical University Hospital, Saitama 350-0495, Japan.
Giedre GrigelionieneDepartment of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, 17176 Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, 17176 Stockholm, Sweden.
Andrew JacksonMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Monte WesterfieldInstitute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.
Michael B BoberDivision of Orthogenetics, A.I. duPont Hospital for Children, Wilmington, DE, 19803, USA.
William A GahlOffice of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Hudson H FreezeHuman Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
National Human Genome Research Institute · USUniversity of Oregon · USKarolinska Institutet · SENational Institutes of Health · USAmbry Genetics (United States) · USCommunity Health Systems - Dupont Hospital · USDiscovery Institute · USInstitute of Genetics and Cancer · GBKarolinska University Hospital · SEMayo Clinic · USMcMaster Children's Hospital · CARigshospitalet · DKUniversity of Georgia · USVanderbilt University Medical Center · USChildren's Hospital of Los Angeles · USKaiser Permanente · USPrivatsykehuset Haugesund · NORIKEN Center for Integrative Medical Sciences · JPSanford Burnham Prebys Medical Discovery Institute · USSarah Network of Rehabilitation Hospitals · BR

Funding

Human Biochemical GeneticsZIAHG000215 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI GAHL, WILLIAM · 2009 to 2025
$72.6M
Zebrafish FacilityP01HD022486 · NICHD · UNIVERSITY OF OREGON · PI EISEN, JUDITH S · 1987 to 2017
$28.8M
TR&D1: Stem Cell and Induced Pluripotent Stem Cell Resources (Pages 116-134)P41GM103490 · NIGMS · UNIVERSITY OF GEORGIA · PI PIERCE, J. MICHAEL · 2012 to 2018
$13.7M
Zebrafish CoreU54NS093793 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI BELLEN, HUGO J · 2015 to 2022
$7.5M
New Congenital Disorders of Glycosylation: Therapy and ModelsR01DK099551 · NIDDK · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Hudson H. Freeze · 2014 to 2026
$6.7M
Development of high-throughput workflow for glycosphingolipid analysis and annotationR21AI129873 · NIAID · UNIVERSITY OF GEORGIA · PI AOKI, KAZUHIRO, RANZINGER, RENE · 2016 to 2017
$582k
Clinical Pursuits by the NHGRI Office of the Clinical DirectorZIAHG200402 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI GAHL, WILLIAM · 2019 to 2019
$122k
Medical Research Council MC_PC_U127580972Medical Research Council MC_UU_00007/5NIAID NIH HHS R21 AI129873NICHD NIH HHS P01 HD022486NIDDK NIH HHS R01 DK099551NIGMS NIH HHS P41 GM103490NINDS NIH HHS U54 NS093793
6 · The paper itself

Abstract

The conserved oligomeric Golgi (COG) complex is involved in intracellular vesicular transport, and is composed of eight subunits distributed in two lobes, lobe A (COG1-4) and lobe B (COG5-8). We describe fourteen individuals with Saul-Wilson syndrome, a rare form of primordial dwarfism with characteristic facial and radiographic features. All affected subjects harbored heterozygous de novo variants in COG4, giving rise to the same recurrent amino acid substitution (p.Gly516Arg). Affected individuals' fibroblasts, whose COG4 mRNA and protein were not decreased, exhibited delayed anterograde vesicular trafficking from the ER to the Golgi and accelerated retrograde vesicular recycling from the Golgi to the ER. This altered steady-state equilibrium led to a decrease in Golgi volume, as well as morphologic abnormalities with collapse of the Golgi stacks. Despite these abnormalities of the Golgi apparatus, protein glycosylation in sera and fibroblasts from affected subjects was not notably altered, but decorin, a proteoglycan secreted into the extracellular matrix, showed altered Golgi-dependent glycosylation. In summary, we define a specific heterozygous COG4 substitution as the molecular basis of Saul-Wilson syndrome, a rare skeletal dysplasia distinct from biallelic COG4-CDG.

Indexed as

AdultAmino Acid SubstitutionAnimalsAnimals, Genetically ModifiedCell LineChildChild, PreschoolEndoplasmic ReticulumExtracellular MatrixFemaleFibroblastsFragile X SyndromeGlycosylationGolgi ApparatusHeterozygoteHumansCOG4 protein, humanProteoglycansVesicular Transport Proteins

Identifiers

PMID30290151
PMCPMC6174323
OpenAlexW2895694323

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Registered trials

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.