Evidence map›Paper›PMID 42282956›Full record

ArticleFrontiers in immunology2026

A multidisciplinary RNA-guided approach to complement genomic analysis of unsolved patients with an inborn error of immunity.

Willem T K Maassen, Lotte C E T Pape, Tim Niemeijer, Anne-Margriet Heijink, Martine T Meems-Veldhuis, Daniëlle J Boerrigter, Gerben van der Vries, Helga Westers, Lennart F Johansson, Kasper J van der Velde and 8 more

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Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

18 authors.

Willem T K MaassenGenomics Coordination Center, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Lotte C E T PapeDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Tim NiemeijerGenomics Coordination Center, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Anne-Margriet HeijinkDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Martine T Meems-VeldhuisDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Daniëlle J BoerrigterDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Gerben van der VriesGenomics Coordination Center, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Helga WestersDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Lennart F JohanssonGenomics Coordination Center, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Kasper J van der VeldeGenomics Coordination Center, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Morris A SwertzGenomics Coordination Center, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Lude FrankeDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Geertje E LeggerDepartment of Paediatrics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Annechien J A LambeckDepartment of Medical Immunology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Abraham RutgersDepartment of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Iris H JonkersDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Mariëlle E van GijnGenomics Coordination Center, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Evelien Zonneveld-HuijssoonDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Inborn errors of immunity (IEI) comprise a heterogeneous, and growing, group of over 550 disorders linked to over 500 genes. Current diagnostic rates for IEI range from 15-70%, with missed diagnoses likely explained by variants of uncertain significance that lack evidence for reclassification and/or variants undetectable with current methods. To overcome these limitations, we developed a structured, RNA-guided approach to reanalyze unsolved IEI patients and increase the diagnostic yield of genetic testing. Methods: In a multidisciplinary team, we analyzed a cohort of 22 patients suspected to have an IEI for whom standard diagnostic genetic testing was inconclusive. We systematically evaluated whether aberrant expression, aberrant splicing or mono-allelic expression, based on the detection of expression outliers, splicing outliers and allele-specific read counts at heterozygous single nucleotide variants could reveal potentially causative variants that aligned with the clinical phenotype and expected mode of inheritance. Results: In one male patient, we detected a splice variant in Conclusion: We could provide a conclusive diagnosis for 2 out of 22 patients, underscoring how RNA-guided variant interpretation can improve genetic diagnostic yield in IEI patients. With advances in interpretation technologies, integrating RNA-sequencing into routine diagnostics could be a pivotal step toward achieving more comprehensive and precise genetic diagnoses of IEI.

Indexed as

GenomicsImmune System DiseasesFemaleGenetic Predisposition to DiseaseGenetic TestingHumansMalePhenotypeRNA Splicingaberrant gene expressionaberrant splicingdiagnosticsinborn errors of immunitymono-allelic expressionmultidisciplinary teamRNA-sequencing

Identifiers

PMID42282956
PMCPMC13252776

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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.