ArticleAmerican journal of human genetics2021
De novo TRIM8 variants impair its protein localization to nuclear bodies and cause developmental delay, epilepsy, and focal segmental glomerulosclerosis.
Registry-linked trialOpen access · bronzeAbstract read
In one paragraph
Article in American journal of human genetics, 2021. 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 18 papers, 1 of them a synthesis that pooled it.
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0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 14% of its field
What it found
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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.
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.
Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network
Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Genetics in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.Kidney international · 2022Guideline
- TRIM8 Promotes Epileptiform Activity by Destabilizing the Glucocorticoid Receptor NR3C1 and Enhancing AMPA Receptor Phosphorylation.Biomedicines · 2026Article
- Recessive variants in WSB2 encoding a substrate receptor of E3 ubiquitin ligase underlie a neurodevelopmental syndrome.European journal of human genetics : EJHG · 2026Article
- Emerging genetic mechanisms of glomerular proteinuria: a podocyte-centered multi-layer network perspective.Frontiers in genetics · 2026Review
- A nonsense mutation in the Tripartite motif containing 8 (TRIM8) gene, mimicking collagenopathy.Pediatric nephrology (Berlin, Germany) · 2025Article
- Mechanisms of podocyte injury in genetic kidney disease.Pediatric nephrology (Berlin, Germany) · 2025Review
- Hidden genetics behind glomerular scars: an opportunity to understand the heterogeneity of focal segmental glomerulosclerosis?Pediatric nephrology (Berlin, Germany) · 2024Review
- A Rare De Novo Mutation in theInternational journal of molecular sciences · 2024Article
- Novel variants in CRB2 targeting the malfunction of slit diaphragm related to focal segmental glomerulosclerosis.Pediatric nephrology (Berlin, Germany) · 2024Article
- Variants loci and phenotype correlation ofFrontiers in neurology · 2024Article
- Focal segmental glomerulosclerosis and neurogenic bladder in a Chinese patient with a novelSAGE open medical case reports · 2024Article
- De novo truncating variants of TRIM8 and atypical neuro-renal syndrome: a case report and literature review.Italian journal of pediatrics · 2023Review
- State of the art in childhood nephrotic syndrome: concrete discoveries and unmet needs.Frontiers in immunology · 2023Review
- The compound heterozygous mutations of c.607G>a and c.657delC in the FAH gene are associated with renal damage with hereditary tyrosinemia type 1 (HT1).Molecular genetics & genomic medicine · 2023Article
- TTC5 syndrome: Clinical and molecular spectrum of a severe and recognizable condition.American journal of medical genetics. Part A · 2022Article
- Monogenic focal segmental glomerulosclerosis: A conceptual framework for identification and management of a heterogeneous disease.American journal of medical genetics. Part C, Seminars in medical genetics · 2022Review
- Two Children With Steroid-Resistant Significant Proteinuria Due to Nonsense Mutations of theFrontiers in pediatrics · 2022Article
- A novel de novo truncating TRIM8 variant associated with childhood-onset focal segmental glomerulosclerosis without epileptic encephalopathy: a case report.BMC nephrology · 2021Article
Corrections and comments
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Authors and funding
69 authors at 20 institutions in 5 countries.
Patricia L WengDivision of Pediatric Nephrology, UCLA, Los Angeles, CA 90095, USA.
Amar J MajmundarDepartment of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.
Kamal KhanCenter for Disease Modeling, Duke University, Durham, NC 27701, USA; Advanced Center for Translational and Genetic Medicine (ACT-GeM), Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
Tze Y LimDivision of Nephrology, Columbia University, New York, NY 10032, USA.
Shirlee ShrilDepartment of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.
Gina JinDivision of Nephrology, Columbia University, New York, NY 10032, USA.
John MusgroveCenter for Disease Modeling, Duke University, Durham, NC 27701, USA; Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC 27705, USA.
Minxian WangCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Dina F AhramDivision of Nephrology, Columbia University, New York, NY 10032, USA.
Vimla S AggarwalInstitute of Genomic Medicine, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Louise E BierInstitute of Genomic Medicine, Columbia University, New York, NY 10032, USA.
Erin L HeinzenInstitute of Genomic Medicine, Columbia University, New York, NY 10032, USA.
Ana C Onuchic-WhitfordDepartment of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA; Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Nina MannDepartment of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.
Florian BuergerDepartment of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.
Ronen SchneiderDepartment of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.
Konstantin DeutschDepartment of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.
Thomas M KitzlerDepartment of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.
Verena KlämbtDepartment of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.
Amy KolbDepartment of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.
Youying MaoDepartment of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.
Christelle Moufawad El AchkarDivision of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Boston, MA 02115, USA.
Adele MitrottiDivision of Nephrology, Columbia University, New York, NY 10032, USA.
Jeremiah MartinoDivision of Nephrology, Columbia University, New York, NY 10032, USA.
Bodo B BeckInstitute of Human Genetics, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; Center for Molecular Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
Janine AltmüllerCenter for Molecular Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; Cologne Center for Genomics, University of Cologne, 50931 Cologne, Germany.
Marcus R BenzPediatric Nephrology Dachau, 85221 Dachau, Germany.
Shoji YanoGenetics Division, Department of Pediatrics, LAC+USC Medical Center, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Mohamad A MikatiDivision of Pediatric Neurology and Developmental Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Talha GunduzDivision of Pediatric Neurology and Developmental Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Heidi CopeDepartment of Pediatrics, Division of Medical Genetics. Duke University Medical Center, Durham, NC 27710, USA.
Vandana ShashiDepartment of Pediatrics, Division of Medical Genetics. Duke University Medical Center, Durham, NC 27710, USA.
Undiagnosed Diseases Network
Howard TrachtmanDepartment of Pediatrics, Division of Nephrology, New York University Langone Health, New York, NY 10016, USA.
Monica BodriaDivision of Nephrology, Dialysis and Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Giannina Gaslini, 16147 Genova GE, Italy.
Gianluca CaridiDivision of Nephrology, Dialysis and Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Giannina Gaslini, 16147 Genova GE, Italy.
Isabella PisaniU.O. Nefrologia, Azienda Ospedaliero-Universitaria di Parma and Dipartimento di Medicina e Chirurgia, Università di Parma, 43126 Parma PR, Italy.
Enrico FiaccadoriU.O. Nefrologia, Azienda Ospedaliero-Universitaria di Parma and Dipartimento di Medicina e Chirurgia, Università di Parma, 43126 Parma PR, Italy.
Asmaa S AbuMaziadDivision of Pediatric Nephrology, University of Arizona-Tucson, AZ 85724, USA.
Julian A Martinez-AgostoDepartment of Pediatrics, Division of Medical Genetics, UCLA, Los Angeles, CA 90095, USA; Department of Human Genetics, UCLA, Los Angeles, CA 90095, USA; Department of Psychiatry, UCLA, Los Angeles, CA 90095, USA.
Ora YadinDivision of Pediatric Nephrology, UCLA, Los Angeles, CA 90095, USA.
Jonathan ZuckermanDepartment of Pathology and Laboratory Medicine, UCLA, Los Angeles, CA 90095, USA.
Arang KimDepartment of Pediatrics, Division of Medical Genetics, UCLA, Los Angeles, CA 90095, USA.
UCLA Clinical Genomics Center
Ulrike John-KroegelPediatric Nephrology, University Children`s Hospital, 07747 Jena, Germany.
Amanda V TyndallDepartment of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.
Jillian S ParboosinghDepartment of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.
A Micheil InnesDepartment of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.
Agnieszka BierzynskaBristol Renal, University of Bristol and Bristol Royal Hospital for Children, Bristol BS2 8BJ, UK.
Ania B KoziellDepartment of Paediatric Nephrology, Evelina London, London SE1 7EH, UK; Faculty of Life Sciences, King's College London SE1 9RT, UK.
Mordi MuorahRenal Unit, Birmingham Children's Hospital, Birmingham, B4 6NH, UK.
Moin A SaleemBristol Renal, University of Bristol and Bristol Royal Hospital for Children, Bristol BS2 8BJ, UK.
Julia HoefeleInstitute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, 81675 Munich, Germany.
Korbinian M RiedhammerInstitute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, 81675 Munich, Germany; Department of Nephrology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, 81675 Munich, Germany.
Ali G GharaviDivision of Nephrology, Columbia University, New York, NY 10032, USA.
Vaidehi JobanputraDepartment of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA; New York Genome Center, New York, NY 10013, USA.
Emma Pierce-HoffmanBroad Center for Mendelian Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
Eleanor G SeabyBroad Center for Mendelian Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
Anne O'Donnell-LuriaDepartment of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA; Broad Center for Mendelian Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
Heidi L RehmBroad Center for Mendelian Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
Shrikant ManeDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA; Yale Center for Mendelian Genomics, Yale University School of Medicine, New Haven, CT 06520, USA.
Vivette D D'AgatiDepartment of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Martin R PollakDivision of Nephrology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Gian Marco GhiggeriDivision of Nephrology, Dialysis and Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Giannina Gaslini, 16147 Genova GE, Italy.
Richard P LiftonDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA; Yale Center for Mendelian Genomics, Yale University School of Medicine, New Haven, CT 06520, USA; Laboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY 10065, USA.
David B GoldsteinInstitute of Genomic Medicine, Columbia University, New York, NY 10032, USA.
Erica E DavisCenter for Disease Modeling, Duke University, Durham, NC 27701, USA; Advanced Center for Translational and Genetic Medicine (ACT-GeM), Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA; Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Friedhelm HildebrandtDepartment of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA. Electronic address: friedhelm.hildebrandt@childrens.harvard.edu.
Simone Sanna-CherchiDivision of Nephrology, Columbia University, New York, NY 10032, USA. Electronic address: ss2517@cumc.columbia.edu.
Boston Children's Hospital · USColumbia University · USDuke Medical Center · USIstituto Giannina Gaslini · ITAlberta Children's Hospital · CABristol Royal Hospital for Children · GBBroad Institute · USKlinikum rechts der Isar · DEMassachusetts Institute of Technology · USOspedale di Parma · ITUCLA Health · USUniversity of California, Los Angeles · USBirmingham Children's Hospital · GBBroad Center · USDuke University · USDuke University Hospital · USEvelina London Children's Healthcare · GBHarvard University · USHelios Amper-Klinikum Dachau · DEJena University Hospital · DE
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MClinical and Translational Science AwardUL1TR001873 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI REILLY, MUREDACH P · 2016 to 2025
$99.0MRenal Physiology and Phenotyping CoreP30DK079310 · NIDDK · YALE UNIVERSITY · PI ARONSON, PETER S. · 2008 to 2022
$16.8MJoint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5MYale Center for Mendelian GenomicsUM1HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2016 to 2020
$14.8MAn integrated and diverse genomic medicine program for undiagnosed diseasesU01HG007672 · NHGRI · DUKE UNIVERSITY · PI SHASHI, VANDANA · 2014 to 2022
$13.4MClinical Sequencing Core Facility for the Undiagnosed Diseases Network (UDN)U01HG007942 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI ENG, CHRISTINE · 2014 to 2021
$10.2MThe Child Heath Research CenterK12HD052896 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI Wendy K Chung · 2007 to 2026
$7.9MIntegrating large scale genomics and functional studies to accelerate FSGS/NS discoveryRC2DK122397 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI HILDEBRANDT, FRIEDHELM, POLLAK, MARTIN R. · 2020 to 2024
$7.4MRESEARCH TRAINING IN PEDIATRIC NEPHROLOGYT32DK007726 · NIDDK · CHILDREN'S HOSPITAL BOSTON · PI BRISCOE, DAVID M. · 1994 to 2023
$5.9MIdentification and function of new genes causing childhood nephrotic syndromeR01DK076683 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HILDEBRANDT, FRIEDHELM · 2007 to 2021
$5.3MNHGRI Genome Sequencing Program Coordinating CenterU24HG008956 · NHGRI · RUTGERS, THE STATE UNIV OF N.J. · PI BUYSKE, STEVEN G, MATISE, TARA C. · 2016 to 2020
$4.9MMedical Research Council G0800571Medical Research Council MR/R013942/1NCATS NIH HHS UL1 TR001863NCATS NIH HHS UL1 TR001873NHGRI NIH HHS R01 HG009141NHGRI NIH HHS U01 HG007672NHGRI NIH HHS U01 HG007942NHGRI NIH HHS U24 HG008956NHGRI NIH HHS UM1 HG006504NHGRI NIH HHS UM1 HG008900NICHD NIH HHS K12 HD052896NIDDK NIH HHS P30 DK079310NIDDK NIH HHS R01 DK076683NIDDK NIH HHS RC2 DK122397NIDDK NIH HHS T32 DK007726
Abstract
Focal segmental glomerulosclerosis (FSGS) is the main pathology underlying steroid-resistant nephrotic syndrome (SRNS) and a leading cause of chronic kidney disease. Monogenic forms of pediatric SRNS are predominantly caused by recessive mutations, while the contribution of de novo variants (DNVs) to this trait is poorly understood. Using exome sequencing (ES) in a proband with FSGS/SRNS, developmental delay, and epilepsy, we discovered a nonsense DNV in TRIM8, which encodes the E3 ubiquitin ligase tripartite motif containing 8. To establish whether TRIM8 variants represent a cause of FSGS, we aggregated exome/genome-sequencing data for 2,501 pediatric FSGS/SRNS-affected individuals and 48,556 control subjects, detecting eight heterozygous TRIM8 truncating variants in affected subjects but none in control subjects (p = 3.28 × 10
Indexed as
AdultAnimalsCarrier ProteinsCell LineChildChild, PreschoolCodon, NonsenseDevelopmental DisabilitiesEpilepsyExome SequencingFemaleGlomerulosclerosis, Focal SegmentalHumansIntranuclear SpaceKidneyMaleCarrier ProteinsCodon, NonsenseNerve Tissue ProteinsTRIM8 protein, humanepilepsyFSGSgenomicsmonogenicnuclear bodySRNSTRIM8
Identifiers
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Registered trials
NCT02450851ClinicalTrials.gov
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.