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Cited by 65Genomics and Rare DiseasesMetabolism and Genetic DisordersConnective tissue disorders research

Whole genome sequencing diagnostic yield for paediatric patients with suspected genetic disorders: systematic review, meta-analysis, and GRADE assessment

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Nurchis, Mario Cesare, Altamura, Gerardo, Riccardi, Maria Teresa, Radio, Francesca Clementina, Chillemi, Giovanni, Bertini, Enrico Silvio, Garlasco, Jacopo, Tartaglia, Marco +2 more·2023·Archives of Public Health
DOI 10.1186/s13690-023-01112-4PMC PMC10210272
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Abstract

Background: About 80% of the roughly 7,000 known rare diseases are single gene disorders, about 85% of which are ultra-rare, affecting less than one in one million individuals. NGS technologies, in particular whole genome sequencing (WGS) in paediatric patients suffering from severe disorders of likely genetic origin improve the diagnostic yield allowing targeted, effective care and management. The aim of this study is to perform a systematic review and meta-analysis to assess the effectiveness of WGS, with respect to whole exome sequencing (WES) and/or usual care, for the diagnosis of suspected genetic disorders among the paediatric population. Methods: A systematic review of the literature was conducted querying relevant electronic databases, including MEDLINE, EMBASE, ISI Web of Science, and Scopus from January 2010 to June 2022. A random-effect meta-analysis was run to inspect the diagnostic yield of different techniques. A network meta-analysis was also performed to directly assess the comparison between WGS and WES. Results: Of the 4,927 initially retrieved articles, thirty-nine met the inclusion criteria. Overall results highlighted a significantly higher pooled diagnostic yield for WGS, 38.6% (95% CI: [32.6 – 45.0]), in respect to WES, 37.8% (95% CI: [32.9 – 42.9]) and usual care, 7.8% (95% CI: [4.4 – 13.2]). The meta-regression output suggested a higher diagnostic yield of the WGS compared to WES after controlling for the type of disease (monogenic vs non-monogenic), with a tendency to better diagnostic performances for Mendelian diseases. The network meta-analysis showed a higher diagnostic yield for WGS compared to WES (OR = 1.54, 95%CI: [1.11 – 2.12]). Conclusions: Although whole genome sequencing for the paediatric population with suspected genetic disorders provided an accurate and early genetic diagnosis in a high proportion of cases, further research is needed for evaluating costs, effectiveness, and cost-effectiveness of WGS and achieving an informed decision-making process. Trial Registration: This systematic review has not been registered.

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  • Whole genome sequencing achieves a diagnostic yield of 38.6% compared with 7.8% for first-tier genetic testing/chromosome microarray analysis.

    “It achieves a diagnostic yield of 38.6% compared to 7.8% with first‐tier genetic testing/chromosome microarray analysis (Nurchis et al., 2023), with particularly high diagnostic yields for intellectual disability.”

    From "I don't grieve as much as I used to": A qualitative study on parents of children with rare and undiagnosed conditions navigating grief in the context of uncertainty. (2025) · cites this paper as Nurchis et al., 2023

    The Results report pooled diagnostic yields of 38.6% for WGS and 7.8% for usual care in paediatric patients with suspected genetic disorders. The Search strategy and selection criteria section lists chromosomal microarray as one example of usual care, alongside other tests. Thus, 7.8% is not a yield specifically for chromosomal microarray or first-tier testing alone. (LLM, conf=0.87)

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Cited by

Sorted by citations

Authors
Nurchis, M. C., Altamura, G., Riccardi, M. T., Radio, F. C., Chillemi, G., Bertini, E. S., Garlasco, J., Tartaglia, M., Dallapiccola, B., & Damiani, G.
Affiliations
  • Università Cattolica del Sacro Cuore (IT)
  • Bambino Gesù Children's Hospital (IT)
  • Università degli Studi della Tuscia (IT)
  • University of Turin (IT)
Corresponding author
Altamura, Gerardo
ORCID
Venue
Archives of Public Health
Publisher
Springer Science and Business Media LLC
Published
2023-05-25
Volume
81
Issue
1
Pages
93-93
ISSN
  • 0778-7367 (ISSN-L)
  • 2049-3258
DOI
10.1186/s13690-023-01112-4
PMC
PMC10210272
OpenAlex
W4378219751
Cited by
65
References
7
Citations by year
2026: 22 · 2025: 22 · 2024: 18 · 2023: 3
FWCI
2.44
Type
journal article
Language
en
Open access
Licence
Locations
  • Archives of Public Health (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubliCatt (Università Cattolica del Sacro Cuore) (submittedVersion, cc-by)
  • Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • UnitusOpen (Tuscia University) (submittedVersion)
Funders
Ministero della Salute (RF-2018–12,366,391, 2018)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
Keywords
whole genome sequencing, exome sequencing, diagnostic yield, rare diseases, monogenic disorders, genetic diagnosis, ultra-rare diseases, usual care comparison

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