De novo TRIM8 variants impair its protein localization to nuclear bodies and cause developmental delay, epilepsy, and focal segmental glomerulosclerosis.

Adult Animals Carrier Proteins / chemistry Cell Line Child Child, Preschool Codon, Nonsense Developmental Disabilities / genetics Epilepsy / genetics Female Glomerulosclerosis, Focal Segmental / genetics Humans Intranuclear Space / metabolism Kidney / metabolism Male Mice Mutation Nephrotic Syndrome / genetics Nerve Tissue Proteins / chemistry Phenotype Podocytes / metabolism Exome Sequencing
FSGS SRNS TRIM8 epilepsy genomics monogenic nuclear body

Journal

American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475

Informations de publication

Date de publication:
04 02 2021
Historique:
received: 27 07 2020
accepted: 11 01 2021
pubmed: 29 1 2021
medline: 20 2 2021
entrez: 28 1 2021
Statut: ppublish

Résumé

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

Identifiants

DOI: 10.1016/j.ajhg.2021.01.008 PMID: 33508234 PMC: PMC7895901
pubmed: 33508234
pii: S0002-9297(21)00008-2
doi: 10.1016/j.ajhg.2021.01.008
pmc: PMC7895901
pii:
doi:

Substances chimiques

Carrier Proteins 0
Codon, Nonsense 0
Nerve Tissue Proteins 0
TRIM8 protein, human 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

357-367

Subventions

Organisme : NHGRI NIH HHS
ID : UM1 HG008900
Pays : United States
Organisme : NIDDK NIH HHS
ID : RC2 DK122397
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG006504
Pays : United States
Organisme : NICHD NIH HHS
ID : K12 HD052896
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK079310
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK076683
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007672
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007726
Pays : United States
Organisme : NHGRI NIH HHS
ID : U24 HG008956
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007942
Pays : United States
Organisme : Medical Research Council
ID : G0800571
Pays : United Kingdom
Organisme : NHGRI NIH HHS
ID : R01 HG009141
Pays : United States
Organisme : Medical Research Council
ID : MR/R013942/1
Pays : United Kingdom
Organisme : NCATS NIH HHS
ID : UL1 TR001873
Pays : United States

Informations de copyright

Copyright © 2021 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

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Auteurs

Patricia L Weng (PL)

Division of Pediatric Nephrology, UCLA, Los Angeles, CA 90095, USA.

Amar J Majmundar (AJ)

Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.

Kamal Khan (K)

Center 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 Lim (TY)

Division of Nephrology, Columbia University, New York, NY 10032, USA.

Shirlee Shril (S)

Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.

Gina Jin (G)

Division of Nephrology, Columbia University, New York, NY 10032, USA.

John Musgrove (J)

Center 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 Wang (M)

Cardiovascular 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 Ahram (DF)

Division of Nephrology, Columbia University, New York, NY 10032, USA.

Vimla S Aggarwal (VS)

Institute 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 Bier (LE)

Institute of Genomic Medicine, Columbia University, New York, NY 10032, USA.

Erin L Heinzen (EL)

Institute of Genomic Medicine, Columbia University, New York, NY 10032, USA.

Ana C Onuchic-Whitford (AC)

Department 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 Mann (N)

Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.

Florian Buerger (F)

Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.

Ronen Schneider (R)

Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.

Konstantin Deutsch (K)

Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.

Thomas M Kitzler (TM)

Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.

Verena Klämbt (V)

Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.

Amy Kolb (A)

Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.

Youying Mao (Y)

Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.

Christelle Moufawad El Achkar (C)

Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Boston, MA 02115, USA.

Adele Mitrotti (A)

Division of Nephrology, Columbia University, New York, NY 10032, USA.

Jeremiah Martino (J)

Division of Nephrology, Columbia University, New York, NY 10032, USA.

Bodo B Beck (BB)

Institute 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 Altmüller (J)

Center 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 Benz (MR)

Pediatric Nephrology Dachau, 85221 Dachau, Germany.

Shoji Yano (S)

Genetics 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 Mikati (MA)

Division of Pediatric Neurology and Developmental Medicine, Duke University Medical Center, Durham, NC 27710, USA.

Talha Gunduz (T)

Division of Pediatric Neurology and Developmental Medicine, Duke University Medical Center, Durham, NC 27710, USA.

Heidi Cope (H)

Department of Pediatrics, Division of Medical Genetics. Duke University Medical Center, Durham, NC 27710, USA.

Vandana Shashi (V)

Department of Pediatrics, Division of Medical Genetics. Duke University Medical Center, Durham, NC 27710, USA.

Howard Trachtman (H)

Department of Pediatrics, Division of Nephrology, New York University Langone Health, New York, NY 10016, USA.

Monica Bodria (M)

Division of Nephrology, Dialysis and Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Giannina Gaslini, 16147 Genova GE, Italy.

Gianluca Caridi (G)

Division of Nephrology, Dialysis and Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Giannina Gaslini, 16147 Genova GE, Italy.

Isabella Pisani (I)

U.O. Nefrologia, Azienda Ospedaliero-Universitaria di Parma and Dipartimento di Medicina e Chirurgia, Università di Parma, 43126 Parma PR, Italy.

Enrico Fiaccadori (E)

U.O. Nefrologia, Azienda Ospedaliero-Universitaria di Parma and Dipartimento di Medicina e Chirurgia, Università di Parma, 43126 Parma PR, Italy.

Asmaa S AbuMaziad (AS)

Division of Pediatric Nephrology, University of Arizona-Tucson, AZ 85724, USA.

Julian A Martinez-Agosto (JA)

Department 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 Yadin (O)

Division of Pediatric Nephrology, UCLA, Los Angeles, CA 90095, USA.

Jonathan Zuckerman (J)

Department of Pathology and Laboratory Medicine, UCLA, Los Angeles, CA 90095, USA.

Arang Kim (A)

Department of Pediatrics, Division of Medical Genetics, UCLA, Los Angeles, CA 90095, USA.

Ulrike John-Kroegel (U)

Pediatric Nephrology, University Children`s Hospital, 07747 Jena, Germany.

Amanda V Tyndall (AV)

Department of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.

Jillian S Parboosingh (JS)

Department of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.

A Micheil Innes (AM)

Department of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.

Agnieszka Bierzynska (A)

Bristol Renal, University of Bristol and Bristol Royal Hospital for Children, Bristol BS2 8BJ, UK.

Ania B Koziell (AB)

Department of Paediatric Nephrology, Evelina London, London SE1 7EH, UK; Faculty of Life Sciences, King's College London SE1 9RT, UK.

Mordi Muorah (M)

Renal Unit, Birmingham Children's Hospital, Birmingham, B4 6NH, UK.

Moin A Saleem (MA)

Bristol Renal, University of Bristol and Bristol Royal Hospital for Children, Bristol BS2 8BJ, UK.

Julia Hoefele (J)

Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, 81675 Munich, Germany.

Korbinian M Riedhammer (KM)

Institute 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 Gharavi (AG)

Division of Nephrology, Columbia University, New York, NY 10032, USA.

Vaidehi Jobanputra (V)

Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA; New York Genome Center, New York, NY 10013, USA.

Emma Pierce-Hoffman (E)

Broad Center for Mendelian Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.

Eleanor G Seaby (EG)

Broad Center for Mendelian Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.

Anne O'Donnell-Luria (A)

Department 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 Rehm (HL)

Broad Center for Mendelian Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.

Shrikant Mane (S)

Department 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'Agati (VD)

Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.

Martin R Pollak (MR)

Division of Nephrology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

Gian Marco Ghiggeri (GM)

Division of Nephrology, Dialysis and Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Giannina Gaslini, 16147 Genova GE, Italy.

Richard P Lifton (RP)

Department 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 Goldstein (DB)

Institute of Genomic Medicine, Columbia University, New York, NY 10032, USA.

Erica E Davis (EE)

Center 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 Hildebrandt (F)

Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA. Electronic address: friedhelm.hildebrandt@childrens.harvard.edu.

Simone Sanna-Cherchi (S)

Division of Nephrology, Columbia University, New York, NY 10032, USA. Electronic address: ss2517@cumc.columbia.edu.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › De novo TRIM8 variants impair its protein...
questionsmedicales.fr › Eucaryotes › Animaux › De novo TRIM8 variants impair its protein...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de transport › De novo TRIM8 variants impair its protein...
questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › De novo TRIM8 variants impair its protein...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › De novo TRIM8 variants impair its protein...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Enfant d'âge préscolaire › De novo TRIM8 variants impair its protein...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Codon non-sens › De novo TRIM8 variants impair its protein...
questionsmedicales.fr › Troubles mentaux › Troubles du développement neurologique › Incapacités de développement › De novo TRIM8 variants impair its protein...
questionsmedicales.fr › Maladies du système nerveux › Maladies du système nerveux central › Encéphalopathies › Épilepsie › De novo TRIM8 variants impair its protein...
questionsmedicales.fr › Maladies urogénitales › Maladies urologiques › Maladies du rein › Néphrite › Glomérulonéphrite › Glomérulonéphrite segmentaire et focale › De novo TRIM8 variants impair its protein...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › De novo TRIM8 variants impair its protein...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Structures nucléaires › Espace intranucléaire › De novo TRIM8 variants impair its protein...
questionsmedicales.fr › Appareil urogénital › Voies urinaires › Rein › De novo TRIM8 variants impair its protein...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › De novo TRIM8 variants impair its protein...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › De novo TRIM8 variants impair its protein...
questionsmedicales.fr › Maladies urogénitales › Maladies urologiques › Maladies du rein › Néphrose › Syndrome néphrotique › De novo TRIM8 variants impair its protein...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › De novo TRIM8 variants impair its protein...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › De novo TRIM8 variants impair its protein...
questionsmedicales.fr › Cellules › Cellules épithéliales › Podocytes › De novo TRIM8 variants impair its protein...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ADN › Séquençage du génome entier › Séquençage de l'exome › De novo TRIM8 variants impair its protein...