ArticleEuropean journal of human genetics : EJHG2019
A head-to-head evaluation of the diagnostic efficacy and costs of trio versus singleton exome sequencing analysis.
Article in European journal of human genetics : EJHG, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Use of whole genome sequencing to determine genetic basis of suspected mitochondrial disorders: cohort study.BMJ (Clinical research ed.) · 2021Trial
- Trial
- Type I Interferon Signature is Associated With Lung Disease, Drug-Associated Immune Reactions, and Genetic Variation in Interferon-Linked Pathways in Still Disease.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Best practice recommendations for bioinformatics approaches applied to high-throughput sequencing for rare disease and cancer diagnosis within the UK National Health Service.Journal of medical genetics · 2026Article
- Familial lymphoma and genetic predisposition: an updated review.BMC medical genomics · 2026Review
- Non-Isolated Dandy-Walker Malformation: Exome Sequencing Efficacy and Phenotypic Expansions.Clinical genetics · 2026Article
- Unclassified Inborn Errors of Immunity Patients without any Pathogenic Variant in Targeted Next-Generation Sequencing: Long-Term Follow-up and Whole Exome Sequencing Results.Journal of clinical immunology · 2026Article
- Piloting an Interpretive External Quality Assurance Model for Genomic Testing for Childhood Syndromes and Intellectual Disability.The Journal of molecular diagnostics : JMD · 2026Article
- Genetic and Molecular Characterization of Treacher Collins Syndrome in Three Mexican Families.International journal of molecular sciences · 2026Article
- Artificial intelligence-assisted clinical exome sequencing: Insights and outcomes from 822 pediatric diagnoses.Genetics in medicine open · 2026Article
- Monogenic Findings in Early Pregnancy Loss: Whole-Exome Sequencing Study of Euploid Products of Conception.Balkan journal of medical genetics : BJMG · 2025Article
- Determining the value of genomics in healthcare.Nature medicine · 2025Review
- Clinical use of whole-genome sequencing in children with developmental delay or intellectual disability.BMC medical genomics · 2025Article
- Should recipient parents have access to gamete donors' raw genomic data? Clinical, legal, and ethical considerations.Journal of assisted reproduction and genetics · 2025Article
- Evaluating genome sequencing strategies: trio, singleton, and standard testing in rare disease diagnosis.Genome medicine · 2025Article
- Clinical manifestations of dual-gene variants involving ABCA4 in retinal dystrophies.BMC ophthalmology · 2025Article
- Rapid Whole-Genome Sequencing in Critically Ill Infants and Children with Suspected, Undiagnosed Genetic Diseases: Evolution to a First-Tier Clinical Laboratory Test in the Era of Precision Medicine.Children (Basel, Switzerland) · 2025Review
- Exome sequencing of 18,994 ethnically diverse patients with suspected rare Mendelian disorders.NPJ genomic medicine · 2025Article
- CNVoyant a machine learning framework for accurate and explainable copy number variant classification.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diagnostic exome sequencing (ES) can be performed on the proband only (singleton; sES) or with additional samples, often including both biological parents with the proband (trio; tES). In this study we sought to compare the efficiencies of exome sequencing (ES) by trio (tES) versus singleton (sES) approach, determine costs, and identify factors to consider when deciding on optimal implementation strategies for the diagnosis of monogenic disorders. We undertook ES in 30 trios and analysed each proband's sES and tES data in parallel. Two teams were randomly allocated to either sES or tES analysis for each case and blinded to each other's work. Each task was timed and cost analyses were based on time taken and diagnostic yield. We modelled three scenarios to determine the factors to consider in the implementation of tES. sES diagnosed 11/30 (36.7%) cases and tES identified one additional diagnosis (12/30 (40.0%)). tES obviated the need for Sanger segregation, reduced the number of variants for curation, and had lower cost-per-diagnosis when considering analysis alone. When sequencing costs were included, tES nearly doubled the cost of sES. Reflexing to tES in those who remain undiagnosed after sES was cost-saving over tES in all as first-line. This approach requires a large differential in diagnostic yield between sES and tES for maximal benefit given current sequencing costs. tES may be preferable when scaling up laboratory throughput due to efficiency gains and opportunity cost considerations. Our findings are relevant to clinicians, laboratories and health services considering tES over sES.
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