Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Genome sequencing as a single comprehensive test in molecular diagnosis

European Journal of Human Genetics volume 31, pages 3–4 (2023)Cite this article

Subjects

Exome sequencing has been implemented in molecular diagnostic laboratories for a decade as a first-tier test for developmental disorders. However, for some unique disease entities, complimentary molecular tests are often needed, such as chromosome microarray analysis (CMA), multiplex ligation-dependent probe amplification (MLPA), and droplet digital PCR (ddPCR) for copy number variations (CNVs), methylation assays for imprinting disorders (e.g., Pseudohypoparathyroidism, Silver-Russell syndrome, Beckwith–Wiedemann syndrome, and Angelman syndrome), repeat-primed PCR for repeat expansion diseases, mitochondrial genome sequencing for suspected mitochondrial disorders, and gene panel with deep sequencing for mosaicism. Current stepwise approach may be cost-effective, but time-consuming. With the molecular basis being identified for more than 6,100 Mendelian disorders (https://www.omim.org/statistics/geneMap) and the concomitant reduction in sequencing costs, genome sequencing (GS) has become as a rapid testing approach to enable early implementation of precision medicine [1]. As most rare Mendelian disorders are either congenital or childhood onset, early molecular diagnosis could shorten the diagnostic odyssey, inform the clinical management, reduce healthcare costs, facilitate genetics counseling regarding the long-term prognosis and recurrence risk.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

References

  1. Petrikin JE, Willig LK, Smith LD, Kingsmore SF. Rapid whole genome sequencing and precision neonatology. Semin Perinatol. 2015;39:623–31.

    Article  Google Scholar 

  2. van der Sanden B, Schobers G, Corominas Galbany J, Koolen DA, Sinnema M, van Reeuwijk J, et al. The performance of genome sequencing as a first-tier test for neurodevelopmental disorders. Eur J Hum Genet. 2022.

  3. Collins RL, Brand H, Redin CE, Hanscom C, Antolik C, Stone MR, et al. Defining the diverse spectrum of inversions, complex structural variation, and chromothripsis in the morbid human genome. Genome Biol. 2017;18:36.

    Article  Google Scholar 

  4. Whiffin N, Karczewski KJ, Zhang X, Chothani S, Smith MJ, Evans DG, et al. Characterising the loss-of-function impact of 5’ untranslated region variants in 15,708 individuals. Nat Commun. 2020;11:2523.

    Article  Google Scholar 

  5. Cummings BB, Marshall JL, Tukiainen T, Lek M, Donkervoort S, Foley AR, et al. Improving genetic diagnosis in Mendelian disease with transcriptome sequencing. Sci Transl Med. 2017;9:eaal5209.

Download references

Funding

None.

Author information

Authors and Affiliations

  1. Center for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Dong Li

  2. Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Dong Li

  3. Division of Human Genetics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Dong Li

Authors
  1. Dong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dong Li.

Ethics declarations

Competing interests

The author declares no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Li, D. Genome sequencing as a single comprehensive test in molecular diagnosis. Eur J Hum Genet 31, 3–4 (2023). https://doi.org/10.1038/s41431-022-01215-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41431-022-01215-6

This article is cited by

Search

Advanced search

Quick links