Trial reportAnnals of neurology2020
Randomized Clinical Trial of First-Line Genome Sequencing in Pediatric White Matter Disorders.
Trial report in Annals of neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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.
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.
Who cites it
17 citing papers in PubMed.
- Normative modeling for quantitative brain MRI phenotyping and biomarker discovery for pediatric leukodystrophies.medRxiv : the preprint server for health sciences · 2026Article
- BLOC1S1 variants cause lysosomal and autophagic defects resulting in a hypomyelinating leukodystrophy with epileptic encephalopathy.American journal of human genetics · 2026Article
- Spectrum of Leukodystrophy and Genetic Leukoencephalopathy in Indian Population Diagnosed by Clinical Exome Sequencing and Clinical Utility.Neurology. Genetics · 2024Article
- Anything is better than nothing': exploring attitudes towards novel therapies in leukodystrophy clinical trials.Orphanet journal of rare diseases · 2024Article
- Longitudinal natural history studies based on real-world data in rare diseases: Opportunity and a novel approach.Molecular genetics and metabolism · 2024Review
- Approaches to diagnosis for individuals with a suspected inherited white matter disorder.Handbook of clinical neurology · 2024Review
- High genetic heterogeneity of leukodystrophies in Iranian children: the first report of Iranian Leukodystrophy Registry.Neurogenetics · 2023Article
- Reactive gene curation to support interpretation and reporting of a clinical genome test for rare disease: Experience from over 1,000 cases.Cell genomics · 2023Article
- The post-diagnostics world: charting a path for pediatric genomic medicine in the twenty-first century.Pediatric research · 2023Article
- Unclassified white matter disorders: A diagnostic journey requiring close collaboration between clinical and laboratory services.European journal of medical genetics · 2022Article
- Reanalysis of exome negative patients with rare disease: a pragmatic workflow for diagnostic applications.Genome medicine · 2022Article
- Diagnosis of Genetic White Matter Disorders by Singleton Whole-Exome and Genome Sequencing Using Interactome-Driven Prioritization.Neurology · 2022Article
- Genome sequencing identifies three molecular diagnoses including a mosaic variant in theCold Spring Harbor molecular case studies · 2021Article
- Clinical and genetic spectrum of 104 Indian families with central nervous system white matter abnormalities.Clinical genetics · 2021Article
- ACER3-related leukoencephalopathy: expanding the clinical and imaging findings spectrum due to novel variants.Human genomics · 2021Article
- Article
- Emerging Concepts in Vector Development for Glial Gene Therapy: Implications for Leukodystrophies.Frontiers in cellular neuroscience · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
31 authors.
Funding
Abstract
objectiveGenome sequencing (GS) is promising for unsolved leukodystrophies, but its efficacy has not been prospectively studied.
methodsA prospective time-delayed crossover design trial of GS to assess the efficacy of GS as a first-line diagnostic tool for genetic white matter disorders took place between December 1, 2015 and September 27, 2017. Patients were randomized to receive GS immediately with concurrent standard of care (SoC) testing, or to receive SoC testing for 4 months followed by GS.
resultsThirty-four individuals were assessed at interim review. The genetic origin of 2 patient's leukoencephalopathy was resolved before randomization. Nine patients were stratified to the immediate intervention group and 23 patients to the delayed-GS arm. The efficacy of GS was significant relative to SoC in the immediate (5/9 [56%] vs 0/9 [0%]; Wild-Seber, p < 0.005) and delayed (control) arms (14/23 [61%] vs 5/23 [22%]; Wild-Seber, p < 0.005). The time to diagnosis was significantly shorter in the immediate-GS group (log-rank test, p = 0.04). The overall diagnostic efficacy of combined GS and SoC approaches was 26 of 34 (76.5%, 95% confidence interval = 58.8-89.3%) in <4 months, greater than historical norms of <50% over 5 years. Owing to loss of clinical equipoise, the trial design was altered to a single-arm observational study.
interpretationIn this study, first-line GS provided earlier and greater diagnostic efficacy in white matter disorders. We provide an evidence-based diagnostic testing algorithm to enable appropriate clinical GS utilization in this population. ANN NEUROL 2020;88:264-273.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.