Evidence map›Paper›PMID 35211795›Full record

ArticlePediatric nephrology (Berlin, Germany)2022

Exploring the relevance of NUP93 variants in steroid-resistant nephrotic syndrome using next generation sequencing and a fly kidney model.

Agnieszka Bierzynska, Katherine Bull, Sara Miellet, Philip Dean, Chris Neal, Elizabeth Colby, Hugh J McCarthy, Shivaram Hegde, Manish D Sinha, Carmen Bugarin Diz and 14 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pediatric nephrology (Berlin, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

12 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Nucleoporin-associated steroid-resistant nephrotic syndrome.Pediatric nephrology (Berlin, Germany) · 2025
    Review
  7. Advances in the understanding of nuclear pore complexes in human diseases.Journal of cancer research and clinical oncology · 2024
    Review
  8. Article
  9. Article
  10. Insights into human kidney function from the study of Drosophila.Pediatric nephrology (Berlin, Germany) · 2023
    Review
  11. Steroid-Resistant Nephrotic Syndrome Caused byJournal of clinical medicine · 2023
    Article
  12. A rare cause of steroid-resistant nephrotic syndrome - a case report.Central-European journal of immunology · 2023
    Article
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

24 authors at 11 institutions in 2 countries.

Agnieszka BierzynskaBristol Renal and Children's Renal Unit, Bristol Medical School, University of Bristol, Whitson Street, Bristol, BS1 3NY, UK.
Katherine BullNuffield Department of Medicine, University of Oxford, Oxford, UK.
Sara MielletDepartment of Life and Environmental Science, Bournemouth University, Talbot Campus, Fern Barrow, Poole, Dorset, BH12 5BB, England, UK.
Philip DeanBristol Genetics Laboratory, North Bristol National Health Service Trust, Bristol, UK.
Chris NealBristol Renal and Children's Renal Unit, Bristol Medical School, University of Bristol, Whitson Street, Bristol, BS1 3NY, UK.
Elizabeth ColbyBristol Renal and Children's Renal Unit, Bristol Medical School, University of Bristol, Whitson Street, Bristol, BS1 3NY, UK.
Hugh J McCarthyBristol Renal and Children's Renal Unit, Bristol Medical School, University of Bristol, Whitson Street, Bristol, BS1 3NY, UK.
Shivaram HegdeChildren's Kidney Centre, University Hospital of Wales, Cardiff, UK.
Manish D SinhaDepartment of Paediatric Nephrology, Evelina London Children's Hospital, Guy's and St, Thomas' Hospital, London, UK.
Carmen Bugarin DizSchool of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, SE1 7EH, UK.
Kathleen StirrupsNIHR BioResource, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Karyn MegyNIHR BioResource, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Rutendo MapetaNIHR BioResource, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Chris PenkettNIHR BioResource, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Sarah MarshBristol Genetics Laboratory, North Bristol National Health Service Trust, Bristol, UK.
Natalie ForresterIllawarra Health and Medical Research Institute, Molecular Horizons and School of Medicine, University of Wollongong, Wollongong, Australia.
Maryam AfzalBristol Renal and Children's Renal Unit, Bristol Medical School, University of Bristol, Whitson Street, Bristol, BS1 3NY, UK.
Hannah StarkNIHR BioResource, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Nihr BioResourceNIHR BioResource, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Maggie WilliamsBristol Genetics Laboratory, North Bristol National Health Service Trust, Bristol, UK.
Gavin I WelshBristol Renal and Children's Renal Unit, Bristol Medical School, University of Bristol, Whitson Street, Bristol, BS1 3NY, UK.
Ania B Koziell *Department of Paediatric Nephrology, Evelina London Children's Hospital, Guy's and St, Thomas' Hospital, London, UK.
Paul S Hartley *Department of Life and Environmental Science, Bournemouth University, Talbot Campus, Fern Barrow, Poole, Dorset, BH12 5BB, England, UK.
Moin A Saleem *Bristol Renal and Children's Renal Unit, Bristol Medical School, University of Bristol, Whitson Street, Bristol, BS1 3NY, UK. M.Saleem@bristol.ac.uk.ORCID 0000-0002-9808-4518
Cambridge University Hospitals NHS Foundation Trust · GBUniversity of Bristol · GBNational Health Service · GBSt Thomas' Hospital · GBUniversity of Wollongong · AUAt Bristol · GBBournemouth University · GBChildren's Hospital at Westmead · AUKing's College London · GBUniversity Hospital of Wales · GBUniversity of Oxford · GB

Funding

British Heart FoundationDepartment of Health RG65966Medical Research Council MR/R007748/1Medical Research Council MR/R013942/1Medical Research Council MR/RO13942/1
6 · The paper itself

Abstract

backgroundVariants in genes encoding nuclear pore complex (NPC) proteins are a newly identified cause of paediatric steroid-resistant nephrotic syndrome (SRNS). Recent reports describing NUP93 variants suggest these could be a significant cause of paediatric onset SRNS. We report NUP93 cases in the UK and demonstrate in vivo functional effects of Nup93 depletion in a fly (Drosophila melanogaster) nephrocyte model.

methodsThree hundred thirty-seven paediatric SRNS patients from the National cohort of patients with Nephrotic Syndrome (NephroS) were whole exome and/or whole genome sequenced. Patients were screened for over 70 genes known to be associated with Nephrotic Syndrome (NS). D. melanogaster Nup93 knockdown was achieved by RNA interference using nephrocyte-restricted drivers.

resultsSix novel homozygous and compound heterozygous NUP93 variants were detected in 3 sporadic and 2 familial paediatric onset SRNS characterised histologically by focal segmental glomerulosclerosis (FSGS) and progressing to kidney failure by 12 months from clinical diagnosis. Silencing of the two orthologs of human NUP93 expressed in D. melanogaster, Nup93-1, and Nup93-2 resulted in significant signal reduction of up to 82% in adult pericardial nephrocytes with concomitant disruption of NPC protein expression. Additionally, nephrocyte morphology was highly abnormal in Nup93-1 and Nup93-2 silenced flies surviving to adulthood.

conclusionWe expand the spectrum of NUP93 variants detected in paediatric onset SRNS and demonstrate its incidence within a national cohort. Silencing of either D. melanogaster Nup93 ortholog caused a severe nephrocyte phenotype, signaling an important role for the nucleoporin complex in podocyte biology. A higher resolution version of the Graphical abstract is available as Supplementary information.

Indexed as

Drosophila melanogasterNephrotic SyndromeNuclear Pore Complex ProteinsPodocytesAdultAnimalsChildDisease Models, AnimalDrug ResistanceGlucocorticoidsHigh-Throughput Nucleotide SequencingHumansMutationGlucocorticoidsNuclear Pore Complex ProteinsNup93 protein, humanFSGSNephrocyteNUP93PodocyteSRNS

Identifiers

PMID35211795
PMCPMC9489583
OpenAlexW4213425842

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.