Trial reportBMJ (Clinical research ed.)2021
Use of whole genome sequencing to determine genetic basis of suspected mitochondrial disorders: cohort study.
Trial report in BMJ (Clinical research ed.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
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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
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Whole genome sequencing diagnostic yield for paediatric patients with suspected genetic disorders: systematic review, meta-analysis, and GRADE assessment.Archives of public health = Archives belges de sante publique · 2023Pooled it
- Advances in diagnosis of mitochondrial dysfunction and primary mitochondrial disease.Disease models & mechanisms · 2026Review
- Advances in Primary Mitochondrial Diseases: Diagnosis, Natural History Studies and Clinical Trials.Genes · 2026Review
- Systematic reanalysis of next-generation sequencing data in 101 neuromuscular disorder families enhances diagnostic yield, reveals intronic variants, and identifies a novel disease gene.Journal of neurology · 2026Article
- Screening and Stratification Utility of GDF-15 and FGF-21 in Individuals Evaluated for Suspected Mitochondrial Disease: A Malaysian Cohort Study.Metabolites · 2026Article
- Mainstreaming genomic testing for mitochondrial disease in Australia.European journal of human genetics : EJHG · 2026Article
- Cooperative Architecture of Mitochondrial Proteome Homeostasis.medRxiv : the preprint server for health sciences · 2026Article
- Identification of Intronic Variants inNeurology. Genetics · 2026Article
- From Congenital Torticollis to Leigh Syndrome: A Case Report of Diagnostic Evolution in an Infant.Children (Basel, Switzerland) · 2025Article
- Mitochondrial DNA Replication and Disease: A Historical Perspective on Molecular Insights and Therapeutic Advances.International journal of molecular sciences · 2025Review
- Mitochondrial DNA variant detection in over 6,500 rare disease families by the systematic analysis of exome and genome sequencing data resolves undiagnosed cases.HGG advances · 2025Article
- Mitochondrial DNA disease discovery through evaluation of genotype and phenotype data: The Solve-RD experience.American journal of human genetics · 2025Article
- Long term follow-up of multiorgan disease in Kleefstra syndrome 2 in an adult - case report.BMC neurology · 2025Article
- Systematic genetic assessment of hearing loss using whole-genome sequencing identifies pathogenic variants.Experimental & molecular medicine · 2025Article
- De NovoInternational journal of molecular sciences · 2025Review
- Rapid whole genome sequencing in newborn screening for metabolic diseases.Frontiers in pediatrics · 2025Review
- Artificial intelligence in variant calling: a review.Frontiers in bioinformatics · 2025Review
- The potential clinical utility of Whole Genome Sequencing for patients with cancer: evaluation of a regional implementation of the 100,000 Genomes Project.British journal of cancer · 2024Article
- Article
- Cardiomyopathies in 100,000 genomes project: interval evaluation improves diagnostic yield and informs strategies for ongoing gene discovery.Genome medicine · 2024Article
Corrections and comments
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Authors and funding
31 authors at 12 institutions in 2 countries.
Funding
Abstract
objectiveTo determine whether whole genome sequencing can be used to define the molecular basis of suspected mitochondrial disease.
designCohort study.
settingNational Health Service, England, including secondary and tertiary care.
participants345 patients with suspected mitochondrial disorders recruited to the 100 000 Genomes Project in England between 2015 and 2018.
interventionShort read whole genome sequencing was performed. Nuclear variants were prioritised on the basis of gene panels chosen according to phenotypes, ClinVar pathogenic/likely pathogenic variants, and the top 10 prioritised variants from Exomiser. Mitochondrial DNA variants were called using an in-house pipeline and compared with a list of pathogenic variants. Copy number variants and short tandem repeats for 13 neurological disorders were also analysed. American College of Medical Genetics guidelines were followed for classification of variants.
main outcome measureDefinite or probable genetic diagnosis.
resultsA definite or probable genetic diagnosis was identified in 98/319 (31%) families, with an additional 6 (2%) possible diagnoses. Fourteen of the diagnoses (4% of the 319 families) explained only part of the clinical features. A total of 95 different genes were implicated. Of 104 families given a diagnosis, 39 (38%) had a mitochondrial diagnosis and 65 (63%) had a non-mitochondrial diagnosis.
conclusionWhole genome sequencing is a useful diagnostic test in patients with suspected mitochondrial disorders, yielding a diagnosis in a further 31% after exclusion of common causes. Most diagnoses were non-mitochondrial disorders and included developmental disorders with intellectual disability, epileptic encephalopathies, other metabolic disorders, cardiomyopathies, and leukodystrophies. These would have been missed if a targeted approach was taken, and some have specific treatments.
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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.