Evidence map›Paper›PMID 34010604›Full record

ArticleAmerican journal of human genetics2021

Bi-allelic variants in IPO8 cause a connective tissue disorder associated with cardiovascular defects, skeletal abnormalities, and immune dysregulation.

Alban Ziegler, Rémi Duclaux-Loras, Céline Revenu, Fabienne Charbit-Henrion, Bernadette Begue, Karine Duroure, Linda Grimaud, Anne Laure Guihot, Valérie Desquiret-Dumas, Mohammed Zarhrate and 37 more

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PubMed Full text at PMC Publisher
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. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 8% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

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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

47 authors at 20 institutions in 8 countries.

Alban ZieglerDepartment of Biochemistry and Molecular Biology, CHU d'Angers, 49000 Angers, France; University of Angers, MitoVasc, UMR CNRS 6015, INSERM 1083, 49933 Angers, France.
Rémi Duclaux-LorasUniversité de Paris, Imagine Institute, Laboratory of Intestinal Immunity, INSERM, UMR1163, 75015 Paris, France.
Céline RevenuSorbonne Université, INSERM, CNRS, Institut de la Vision, 17 Rue Moreau, 75012 Paris, France; Institut Curie, PSL Research University, INSERM U934, CNRS UMR3215, 75005 Paris, France.
Fabienne Charbit-HenrionUniversité de Paris, Imagine Institute, Laboratory of Intestinal Immunity, INSERM, UMR1163, 75015 Paris, France; Department of Pediatric Gastroenterology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, 75015 Paris, France; Department of Molecular Genetics, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, 75015 Paris, France.
Bernadette BegueUniversité de Paris, Imagine Institute, Laboratory of Intestinal Immunity, INSERM, UMR1163, 75015 Paris, France.
Karine DuroureSorbonne Université, INSERM, CNRS, Institut de la Vision, 17 Rue Moreau, 75012 Paris, France; Institut Curie, PSL Research University, INSERM U934, CNRS UMR3215, 75005 Paris, France.
Linda GrimaudUniversity of Angers, MitoVasc, UMR CNRS 6015, INSERM 1083, 49933 Angers, France.
Anne Laure GuihotUniversity of Angers, MitoVasc, UMR CNRS 6015, INSERM 1083, 49933 Angers, France.
Valérie Desquiret-DumasDepartment of Biochemistry and Molecular Biology, CHU d'Angers, 49000 Angers, France; University of Angers, MitoVasc, UMR CNRS 6015, INSERM 1083, 49933 Angers, France.
Mohammed ZarhrateGenomics Core Facility, Institut Imagine-Structure Fédérative de Recherche Necker, INSERM U1163 et INSERM US24/CNRS UMS3633, Paris Descartes Sorbonne Paris Cité University, 75015 Paris, France.
Nicolas CagnardBioinformatics Core Facility, INSERM-UMR 1163, Imagine Institute, 75015 Paris, France.
Emmanuel MasIRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse 31300, France; Centre de Référence des Maladies Rares Digestives, and Pediatric Clinical Research Unit, Toulouse Clinical Investigation Center INSERM U1436, Hôpital des Enfants, CHU de Toulouse, Toulouse 31300, France.
Anne BretonIRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse 31300, France; Centre de Référence des Maladies Rares Digestives, and Pediatric Clinical Research Unit, Toulouse Clinical Investigation Center INSERM U1436, Hôpital des Enfants, CHU de Toulouse, Toulouse 31300, France.
Thomas EdouardReference Centre for Marfan Syndrome and Reference Centre on Rare Bone Diseases, Pediatric Clinical Research Unit, Children's Hospital, Toulouse University Hospital, RESTORE, INSERM UMR1301, 31300 Toulouse, France.
Clarisse BillonCentre de Génétique, Centre de Référence des Maladies Vasculaires Rares, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, 75015 Paris, France.
Michael FrankCentre de Génétique, Centre de Référence des Maladies Vasculaires Rares, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, 75015 Paris, France.
Estelle ColinDepartment of Biochemistry and Molecular Biology, CHU d'Angers, 49000 Angers, France.
Guy LenaersUniversity of Angers, MitoVasc, UMR CNRS 6015, INSERM 1083, 49933 Angers, France.
Daniel HenrionUniversity of Angers, MitoVasc, UMR CNRS 6015, INSERM 1083, 49933 Angers, France.
Stanislas LyonnetUniversité de Paris, Imagine Institute, Laboratory of Embryology and Genetics of Malformations, INSERM UMR 1163, 75015 Paris, France; Fédération de Génétique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, 75015 Paris, France.
Laurence FaivreCentre de Référence Anomalies du Développement et Syndromes Malformatifs, FHU TRANSLAD, Hôpital d'Enfants, CHU Dijon, 21000 Dijon, France.
Yves AlembikDépartement de Génétique Médicale, CHU de Hautepierre, 67200 Strasbourg, France.
Anaïs PhilippeDépartement de Génétique Médicale, CHU de Hautepierre, 67200 Strasbourg, France.
Bruno MoulinNephrology and Transplantation Department, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, 67200 Strasbourg, France.
Eyal ReinsteinMedical Genetics Institute, Meir Medical Center, Kfar-Saba 4428164, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
Shay TzurGenomic Research Department, Emedgene Technologies, 67443 Tel Aviv, Israel.
Ruben AttaliGenomic Research Department, Emedgene Technologies, 67443 Tel Aviv, Israel.
George McGillivrayVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville 3052, Melbourne, VIC, Australia.
Susan M WhiteVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville 3052, Melbourne, VIC, Australia.
Lyndon GallacherVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville 3052, Melbourne, VIC, Australia; Department of Paediatrics, The University of Melbourne, 3010 Parkville, Melbourne, VIC, Australia.
Kerstin KutscheInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Pauline SchneebergerInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Katta M GirishaDepartment of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576104, India.
Shalini S NayakDepartment of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576104, India.
Lynn PaisBroad Center for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
Reza MaroofianDepartment of Neuromuscular Disorders, Queen Square Institute of Neurology, University College London, WC1N 3BG London, UK.
Aboulfazl RadDepartment of Otolaryngology-Head & Neck Surgery, Tübingen Hearing Research Centre, Eberhard Karls University of Tübingen, 72076 Tübingen, Germany.
Barbara VonaDepartment of Otolaryngology-Head & Neck Surgery, Tübingen Hearing Research Centre, Eberhard Karls University of Tübingen, 72076 Tübingen, Germany; Institute of Human Genetics, Julius Maximilians University Würzburg, 97074 Würzburg, Germany.
Ehsan Ghayoor KarimianiMolecular and Clinical Sciences Institute, St. George's, University of London, Cranmer Terrace London, SW17 ORE London, UK; Innovative Medical Research Center, Mashhad Branch, Islamic Azdad University, Mashhad 9133736351, Iran.
Caroline LekszasInstitute of Human Genetics, Julius Maximilians University Würzburg, 97074 Würzburg, Germany.
Thomas HaafInstitute of Human Genetics, Julius Maximilians University Würzburg, 97074 Würzburg, Germany.
Ludovic MartinUniversity of Angers, MitoVasc, UMR CNRS 6015, INSERM 1083, 49933 Angers, France; Department of Dermatology, CHU d'Angers, 49000 Angers, France.
Frank RuemmeleUniversité de Paris, Imagine Institute, Laboratory of Intestinal Immunity, INSERM, UMR1163, 75015 Paris, France; Department of Pediatric Gastroenterology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, 75015 Paris, France.
Dominique BonneauDepartment of Biochemistry and Molecular Biology, CHU d'Angers, 49000 Angers, France; University of Angers, MitoVasc, UMR CNRS 6015, INSERM 1083, 49933 Angers, France.
Nadine Cerf-BensussanUniversité de Paris, Imagine Institute, Laboratory of Intestinal Immunity, INSERM, UMR1163, 75015 Paris, France.
Filippo Del BeneSorbonne Université, INSERM, CNRS, Institut de la Vision, 17 Rue Moreau, 75012 Paris, France; Institut Curie, PSL Research University, INSERM U934, CNRS UMR3215, 75005 Paris, France. Electronic address: filippo.del-bene@inserm.fr.
Marianna ParlatoUniversité de Paris, Imagine Institute, Laboratory of Intestinal Immunity, INSERM, UMR1163, 75015 Paris, France. Electronic address: marianna.parlato@inserm.fr.
Centre National de la Recherche Scientifique · FRInserm · FRHôpital Necker-Enfants Malades · FRUniversity of Würzburg · DEAssistance Publique – Hôpitaux de Paris · FRBSD Crown (Israel) · ILHôpital d'Hautepierre · FRManipal Academy of Higher Education · INUniversität Hamburg · DEUniversité Toulouse III - Paul Sabatier · FRVictorian Clinical Genetics Services · AUBroad Institute · USCentre Hospitalier Universitaire d'Angers · FRDélégation Paris 5 · FRHôpital d'Enfants · FRHôpitaux Universitaires de Strasbourg · FRNational Hospital for Neurology and Neurosurgery · GBSt George's, University of London · GBTel Aviv University · ILThe University of Melbourne · AU

Funding

Joint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5M
A powerful web-based discovery platform for rare disease geneticsR01HG009141 · NHGRI · BROAD INSTITUTE, INC. · PI QUINLAN, AARON R, REHM, HEIDI L · 2017 to 2020
$2.9M
NHGRI NIH HHS R01 HG009141NHGRI NIH HHS UM1 HG008900
6 · The paper itself

Abstract

Dysregulated transforming growth factor TGF-β signaling underlies the pathogenesis of genetic disorders affecting the connective tissue such as Loeys-Dietz syndrome. Here, we report 12 individuals with bi-allelic loss-of-function variants in IPO8 who presented with a syndromic association characterized by cardio-vascular anomalies, joint hyperlaxity, and various degree of dysmorphic features and developmental delay as well as immune dysregulation; the individuals were from nine unrelated families. Importin 8 belongs to the karyopherin family of nuclear transport receptors and was previously shown to mediate TGF-β-dependent SMADs trafficking to the nucleus in vitro. The important in vivo role of IPO8 in pSMAD nuclear translocation was demonstrated by CRISPR/Cas9-mediated inactivation in zebrafish. Consistent with IPO8's role in BMP/TGF-β signaling, ipo8

Indexed as

Loss of Function MutationLoss of HeterozygosityAdolescentAdultAnimalsbeta KaryopherinsBone DiseasesCardiovascular DiseasesChildConnective Tissue DiseasesFemaleHumansImmunity, CellularInfantMaleMiddle Agedbeta KaryopherinsIPO8 protein, humanTransforming Growth Factor betaarterial dilatationconnective tissue disorderIPO8joint hyperlaxityLoeys-Dietz syndromeTGF-β signaling

Identifiers

PMID34010604
PMCPMC8206386
OpenAlexW3161101548

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

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 OpenQuestion graph.