ArticleClinical genetics2025
First-Tier Versus Last-Tier Trio Whole-Genome Sequencing for the Diagnosis of Pediatric-Onset Rare Diseases.
Article in Clinical genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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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.
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Who cites it
5 citing papers in PubMed.
- Expanding Access to Genome Sequencing: Higher Diagnostic Yield in Self-Referred Participants From the CincyKidsSeq Study and Implications for Hybrid Models of Genetic Service Delivery.Clinical genetics · 2026Article
- Telethon Undiagnosed Disease Program: Structured approach to solving rare childhood-onset genetic diseases.Genetics in medicine open · 2026Article
- Toward Same-Day Genome Sequencing in the Critical Care Setting.The New England journal of medicine · 2025Article
- First-Tier Versus Last-Tier Trio Whole-Genome Sequencing for the Diagnosis of Pediatric-Onset Rare Diseases.Clinical genetics · 2025Article
- Newborn Screening of X-Linked Adrenoleukodystrophy in Italy: Clinical and Biochemical Outcomes from a 4-Year Pilot Study.International journal of neonatal screening · 2025Article
Corrections and comments
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Authors and funding
27 authors.
Funding
Abstract
Despite advances in diagnostics, children with rare genetic disorders still face extended diagnostic odysseys, delaying appropriate clinical management, and placing burdens on families and healthcare resources. Whole-genome sequencing (WGS) offers a more comprehensive interrogation of the genome than other genetic tests, but its use in clinical practice remains limited. This study compared diagnostic rates, turnaround times, and clinical utility of first-tier versus last-tier trio-WGS for patients with suspected genetic pediatric-onset conditions, including 97 critical and 104 non-critical patients. Eighty-five patients (42.3%), including 57 (58.8%) critical and 28 (26.9%) non-critical patients, received a molecular diagnosis. The diagnostic rate was higher for first-tier (57%) than for last-tier (32.8%) trio-WGS. Of 121 causative variants identified, 19.8% would have been missed by whole-exome sequencing. Laboratory processing time was 4 days for all patients. The clinical setting had the greatest impact on time to reporting, averaging 5 days for critical patients versus 74 days for outpatients. WGS results impacted clinical decision-making for 34% of all critical and 14.3% of WGS-positive non-critical patients. This is the first Italian clinical study to demonstrate the diagnostic and clinical utility of a genome-first approach for both critical and non-critical patients with suspected genetic pediatric-onset disorders and feasibility in a public healthcare system.
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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.