Evidence map›Paper›PMID 42830293›Full record

Trial reportGenome medicine2026

A nationwide prospective randomized trial for diagnosing developmental disorders demonstrates genome sequencing outperforms standard of care.

Mathilde Geysens, Erika Souche, Maria Chiara Baroni, Valérie Benoit, Tessi Beyltjens, Wouter Bossuyt, Vincent Bours, Marian Crabbé, Didier Croes, Matthias De Smet and 27 more

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Genome medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07051213 (The Belgian Genome Resource to Resolve Rare Diseases), which is not on this 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.

NCT07051213 nacompletednot on this map

The Belgian Genome Resource to Resolve Rare Diseases

TypeinterventionalSponsorUniversitaire Ziekenhuizen KU LeuvenRan2021 to 2025Enrolled567ConditionsIntellectual Developmental Disorder, Malformations, Dysmorphia, Developmental Delay (Disorder)ArmsWhole exome sequencing, Whole genome Sequencing
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

37 authors.

Mathilde GeysensCenter for Human Genetics, University Hospitals Leuven, Leuven, 3000, Belgium.
Erika SoucheCenter for Human Genetics, University Hospitals Leuven, Leuven, 3000, Belgium.
Maria Chiara BaroniCenter for Human Genetics, University Hospitals Leuven, Leuven, 3000, Belgium.
Valérie BenoitCentre de Génétique Humaine, Institut de Pathologie et de Génétique, Gosselies, 6041, Belgium.
Tessi BeyltjensCenter of Medical Genetics, Antwerp University Hospital/University of Antwerp, Edegem, 2650, Belgium.
Wouter BossuytCenter for Human Genetics, University Hospitals Leuven, Leuven, 3000, Belgium.
Vincent BoursService de Génétique Humaine, Centre Hospitalier Universitaire de Liège, Liège, 4000, Belgium.
Marian CrabbéCenter for Human Genetics, University Hospitals Leuven, Leuven, 3000, Belgium.
Didier CroesCenter for Human Genetics, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, 1200, Belgium.
Matthias De SmetCenter for Medical Genetics, Ghent University Hospital, Ghent, 9000, Belgium.
Julie DésirCentre de Génétique Humaine, Institut de Pathologie et de Génétique, Gosselies, 6041, Belgium.
Koenraad DevriendtCenter for Human Genetics, University Hospitals Leuven, Leuven, 3000, Belgium.
Annelies DheedeneCenter for Medical Genetics, Ghent University Hospital, Ghent, 9000, Belgium.
Boyan Ivanov DimitrovVrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Clinical Sciences, Research group Genetics, Reproduction and Development, Centre for Medical Genetics, Brussels, 1090, Belgium.
Katrien JanssensCenter of Medical Genetics, Antwerp University Hospital/University of Antwerp, Edegem, 2650, Belgium.
Candy KumpsCenter for Medical Genetics, Ghent University Hospital, Ghent, 9000, Belgium.
Aimé LumakaService de Génétique Humaine, Centre Hospitalier Universitaire de Liège, Liège, 4000, Belgium.
Björn MentenCenter for Medical Genetics, Ghent University Hospital, Ghent, 9000, Belgium.
Marije MeuwissenCenter of Medical Genetics, Antwerp University Hospital/University of Antwerp, Edegem, 2650, Belgium.
Olivier MonestierCentre de Génétique Humaine, Institut de Pathologie et de Génétique, Gosselies, 6041, Belgium.
Geert MortierCenter for Human Genetics, University Hospitals Leuven, Leuven, 3000, Belgium.
Catharina OlsenVrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Clinical Sciences, Research group Genetics, Reproduction and Development, Centre for Medical Genetics, Brussels, 1090, Belgium.
Leonor PalmeiraService de Génétique Humaine, Centre Hospitalier Universitaire de Liège, Liège, 4000, Belgium.
Hilde PeetersCenter for Human Genetics, University Hospitals Leuven, Leuven, 3000, Belgium.
Laura PölslerVrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Clinical Sciences, Research group Genetics, Reproduction and Development, Centre for Medical Genetics, Brussels, 1090, Belgium.
Nicole RevencuCenter for Human Genetics, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, 1200, Belgium.
Dominique RolandCentre de Génétique Humaine, Institut de Pathologie et de Génétique, Gosselies, 6041, Belgium.
Julie SobletDepartment of Genetics, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Brussels, 1020, Belgium.
Yves SznajerCenter for Human Genetics, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, 1200, Belgium.
Sylvia TaziauxService de Génétique Humaine, Centre Hospitalier Universitaire de Liège, Liège, 4000, Belgium.
Hilde Van EschCenter for Human Genetics, University Hospitals Leuven, Leuven, 3000, Belgium.
Geert VandeweyerCenter of Medical Genetics, Antwerp University Hospital/University of Antwerp, Edegem, 2650, Belgium.
Elise VantroysVrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Clinical Sciences, Research group Genetics, Reproduction and Development, Centre for Medical Genetics, Brussels, 1090, Belgium.
Catherline VilainDepartment of Genetics, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Brussels, 1020, Belgium.
Elsa WiameCenter for Human Genetics, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, 1200, Belgium.
Kris Van Den BogaertCenter for Human Genetics, University Hospitals Leuven, Leuven, 3000, Belgium. kris.vandenbogaert@uzleuven.be.
Joris Robert VermeeschCenter for Human Genetics, University Hospitals Leuven, Leuven, 3000, Belgium. joris.vermeesch@uzleuven.be.

Funding

Fonds Wetenschappelijk Onderzoek T-003819NKU Leuven C1-C14/22/125
6 · The paper itself

Abstract

backgroundExome (ES) or genome (GS) sequencing are recommended as first- or second-tier molecular tests for patients with developmental disorders (DD), but the clinical utility of GS continues to be debated.

methodsThis prospective randomized trial involving all Belgian human genetics centers compared the standard of care (SoC) - combining ES and chromosomal microarray analysis or shallow GS - with GS for 567 individuals with unexplained DD. The study was retrospectively registered.

resultsThe diagnostic yield of GS was 39.8% (113/284) vs. 30% for SoC (85/283) (p = 0.015), mainly due to an increased detection of single nucleotide variants and indels (+ 8.7%). GS also enabled the detection of three non-coding (potential) pathogenic variants. Across both study arms, the diagnostic yield was higher for females (45.5%, 97/213) compared to males (28.5%, 101/354) (p < 0.001). Upon correction for the sex distribution and analytical differences between the study arms, the diagnostic yield difference between GS and SoC was reduced to 7.3% (p = 0.069). De novo variants were found for 23.6% of patients. Analysis of inherited variants in genes associated with autosomal dominant phenotypes contributed more to the diagnostic yield (3.9%) than X-linked variants (1.9%), and to a similar extent as autosomal recessive variants (4.1%).

conclusionsThis nationwide study indicates GS outperforms SoC for the diagnosis of patients with DD in a decentralized hospital setting and well-characterized cohort. The results also highlight the importance of evaluating autosomal dominant inherited variants in genomics analyses for DD.

trial registrationClinicalTrials.gov (NCT07051213, 03-07-2025).

Indexed as

Developmental DisabilitiesStandard of CareWhole Genome SequencingChildChild, PreschoolExome SequencingFemaleGenetic TestingGenome, HumanHumansMaleProspective StudiesCongenital anomaliesDevelopmental disordersDiagnostic yieldExome sequencingGenome sequencingIntellectual disability

Identifiers

PMID42830293
PMCPMC13637178

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