Evidence map›Paper›PMID 34010605›Full record

ArticleAmerican journal of human genetics2021

A human importin-β-related disorder: Syndromic thoracic aortic aneurysm caused by bi-allelic loss-of-function variants in IPO8.

Ilse Van Gucht, Josephina A N Meester, Jotte Rodrigues Bento, Maaike Bastiaansen, Jarl Bastianen, Ilse Luyckx, Lotte Van Den Heuvel, Cédric H G Neutel, Pieter-Jan Guns, Mandy Vermont and 38 more

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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 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

11 citing papers in PubMed, 17 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

48 authors at 16 institutions in 6 countries.

Ilse Van GuchtCenter of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem 2650, Belgium.
Josephina A N MeesterCenter of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem 2650, Belgium.
Jotte Rodrigues BentoCenter of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem 2650, Belgium.
Maaike BastiaansenCenter of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem 2650, Belgium.
Jarl BastianenCenter of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem 2650, Belgium.
Ilse LuyckxCenter of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem 2650, Belgium; Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen 6525 GA, the Netherlands.
Lotte Van Den HeuvelCenter of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem 2650, Belgium.
Cédric H G NeutelLaboratory of Physiopharmacology, University of Antwerp, Antwerp 2610, Belgium.
Pieter-Jan GunsLaboratory of Physiopharmacology, University of Antwerp, Antwerp 2610, Belgium.
Mandy VermontLaboratory of Physiopharmacology, University of Antwerp, Antwerp 2610, Belgium.
Erik FransenCenter of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem 2650, Belgium; StatUa Center for Statistics, University of Antwerp, Antwerp 2000, Belgium.
Melanie H A M PerikCenter of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem 2650, Belgium.
Joe Davis VelchevCenter of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem 2650, Belgium.
Maaike AlaertsCenter of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem 2650, Belgium.
Dorien SchepersCenter of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem 2650, Belgium; Laboratory of Molecular, Cellular and Network Excitability, Department of Biomedical Sciences, University of Antwerp, Antwerp 2610, Belgium.
Silke PeetersCenter of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem 2650, Belgium.
Isabel PintelonLaboratory of Cell Biology & Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp 2610, Belgium.
Abdulrahman AlmesnedPrince Sultan Cardiac Centre, Qassim 31982, Saudi Arabia.
Matteo P FerlaNIHR Oxford Biomedical Research Centre, Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Jenny C TaylorNIHR Oxford Biomedical Research Centre, Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Anthony R DallossoBristol Genetics Laboratory, South West Genomic Laboratory Hub, Southmead Hospital, Bristol BS10 5NB, UK.
Maggie WilliamsBristol Genetics Laboratory, South West Genomic Laboratory Hub, Southmead Hospital, Bristol BS10 5NB, UK.
Julie EvansBristol Genetics Laboratory, South West Genomic Laboratory Hub, Southmead Hospital, Bristol BS10 5NB, UK.
Genomics England Research Consortium
Jill A RosenfeldDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Genetics Laboratories, Houston, TX 77021, USA.
Thierry SluysmansDepartment of Pediatric Cardiology, Cliniques Universitaires Saint-Luc, University of Louvain, Brussels 1200, Belgium.
Desiderio RodriguesBirmingham Women's and Children's Hospital NHS Foundation Trust, Steelhouse Lane, Birmingham B4 6NH, UK.
Ashish ChikermaneBirmingham Women & Children's Hospital, Birmingham B4 6NH, UK.
Gangadhara BharmappanavaraMusgrove Park Hospital, Somerset NHS Foundation Trust, Taunton TA1 5DA, UK.
Kayal VijayakumarDepartment of Paediatric Neurology, University Hospitals Bristol NHS Foundation Trust, Bristol BS2 8BJ, UK.
Hassan Mottaghi Moghaddam ShahriPediatric Department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad 009851, Iran.
Narges HashemiDepartment of Pediatric Neurology, School of Medicine, Mashhad University of Medical Sciences, Mashhad 009851, Iran.
Paria Najarzadeh TorbatiDepartment of Molecular Genetics, Next Generation Genetic Polyclinic, Mashhad University of Medical Sciences, Mashhad 009851, Iran.
Mehran B ToosiDepartment of Pediatric Neurology, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad 009851, Iran.
Zuhair N Al-HassnanCardiovascular Genetic Program, Department of Medical Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh 11564, Saudi Arabia.
Julie VogtWest Midlands Regional Genetics Service, Birmingham Women's and Children's Hospital, Birmingham, B15 2TG, UK.
Nicole RevencuCenter for Human Genetics, Cliniques Universitaires Saint-Luc, University of Louvain, Brussels 1200, Belgium.
Isabelle MaystadtCentre de Génétique Humaine, Institut de Pathologie et de Génétique, Gosselies (Charleroi) 6041, Belgium.
Erin M MillerThe Heart Institute, Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
K Nicole WeaverDivision of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Amber BegtrupGeneDx, Gaithersburg, MD 20877, USA.
Henry HouldenDepartment of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.
David MurphyDepartment of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Reza MaroofianDepartment of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Alistair T PagnamentaNIHR Oxford Biomedical Research Centre, Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Lut Van LaerCenter of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem 2650, Belgium.
Bart L LoeysCenter of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem 2650, Belgium; Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen 6525 GA, the Netherlands. Electronic address: bart.loeys@uantwerpen.be.
Aline VerstraetenCenter of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem 2650, Belgium. Electronic address: aline.verstraeten@uantwerpen.be.
University of Antwerp · BEMashhad University of Medical Sciences · IRCentre for Human Genetics · GBNational Hospital for Neurology and Neurosurgery · GBSouthmead Hospital · GBCincinnati Children's Hospital Medical Center · USCliniques Universitaires Saint-Luc · BERadboud University Nijmegen · NLBaylor College of Medicine · USBirmingham Women’s and Children’s NHS Foundation Trust · GBBirmingham Women's Hospital · GBInstitute of Pathology and Genetics · BEKing Faisal Specialist Hospital & Research Centre · SAMusgrove Park Hospital · GBSaud Al-babtain Cardiac Centre · SAUniversity Hospitals Bristol NHS Foundation Trust · GB

Funding

Wellcome Trust
6 · The paper itself

Abstract

Importin 8, encoded by IPO8, is a ubiquitously expressed member of the importin-β protein family that translocates cargo molecules such as proteins, RNAs, and ribonucleoprotein complexes into the nucleus in a RanGTP-dependent manner. Current knowledge of the cargoes of importin 8 is limited, but TGF-β signaling components such as SMAD1-4 have been suggested to be among them. Here, we report that bi-allelic loss-of-function variants in IPO8 cause a syndromic form of thoracic aortic aneurysm (TAA) with clinical overlap with Loeys-Dietz and Shprintzen-Goldberg syndromes. Seven individuals from six unrelated families showed a consistent phenotype with early-onset TAA, motor developmental delay, connective tissue findings, and craniofacial dysmorphic features. A C57BL/6N Ipo8 knockout mouse model recapitulates TAA development from 8-12 weeks onward in both sexes but most prominently shows ascending aorta dilatation with a propensity for dissection in males. Compliance assays suggest augmented passive stiffness of the ascending aorta in male Ipo8

Indexed as

Loss of Function MutationLoss of HeterozygosityPhenotypeAdultAnimalsAortic Aneurysm, Thoracicbeta KaryopherinsChildChild, PreschoolFemaleHumansMaleMiceMice, Inbred C57BLMice, KnockoutPedigreebeta KaryopherinsIPO8 protein, humanTransforming Growth Factor betaimportin 8knockout mouse modelLoeys-Dietz syndromeShprintzen-Goldberg syndromeTGF-betathoracic aortic aneurysm

Identifiers

PMID34010605
PMCPMC8206384
OpenAlexW3162701528

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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.