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. 2023 May;11(5):e2148.
doi: 10.1002/mgg3.2148. Epub 2023 Feb 13.

The current benefit of genome sequencing compared to exome sequencing in patients with developmental or epileptic encephalopathies

Anna Grether  1 , Ivan Ivanovski  1 , Martina Russo  1 , Anaïs Begemann  1 , Katharina Steindl  1 , Lucia Abela  2 , Michael Papik  1 , Markus Zweier  1 , Beatrice Oneda  1 , Pascal Joset  3 , Anita Rauch  1   4   5   6   7
Affiliations

The current benefit of genome sequencing compared to exome sequencing in patients with developmental or epileptic encephalopathies

Anna Grether et al. Mol Genet Genomic Med. 2023 May.

Abstract

Background: As the technology of next generation sequencing rapidly develops and costs are constantly reduced, the clinical availability of whole genome sequencing (WGS) increases. Thereby, it remains unclear what exact advantage WGS offers in comparison to whole exome sequencing (WES) for the diagnosis of genetic diseases using current technologies.

Methods: Trio-WGS was conducted for 20 patients with developmental or epileptic encephalopathies who remained undiagnosed after WES and chromosomal microarray analysis.

Results: A diagnosis was reached for four patients (20%). However, retrospectively all pathogenic variants could have been detected in a WES analysis conducted with today's methods and knowledge.

Conclusion: The additional diagnostic yield of WGS versus WES is currently largely explained by new scientific insights and the general technological progress. Nevertheless, it is noteworthy that whole genome sequencing has greater potential for the analysis of small copy number and copy number neutral variants not seen with WES as well as variants in noncoding regions, especially as potentially more knowledge of the function of noncoding regions arises. We, therefore, conclude that even though today the added value of WGS versus WES seems to be limited, it may increase substantially in the future.

Keywords: diagnostic yield; epileptic encephalopathy; whole exome sequencing; whole genome sequencing.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Summary of genetic findings of 63 index patients.
FIGURE 2
FIGURE 2
Pathogenic complex rearrangement in patient 70855, consisting of an approximately 39 kb de novo microduplication of parts of TMEM255B inserted into MECP2 and a 0.5 kb deletion in the last exon of MECP2. Each panel A‐D shows from top to bottom genomic position (hg19), gene content, copy number calling, BAM depth, and copy number values of calculated probe bins. (a) WGS showing the deletion in MECP2 with sharp boarders (b) WES showing the deletion in MECP2 (c) WGS showing the duplication of parts of TMEM255B on chromosome 13 (d) WES showing the duplication of parts of TMEM255B on chromosome 13. (e) Results of Optical Genome Mapping using the Bionano Inc. Saphyr® device demonstrating a de novo 39 kb insertion into MECP2, likely corresponding to the 39 kb duplicated segment of TMEM255B.
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References

    1. Barbitoff, Y. A. , Polev, D. E. , Glotov, A. S. , Serebryakova, E. A. , Shcherbakova, I. V. , Kiselev, A. M. , Kostareva, A. A. , Glotov, O. S. , & Predeus, A. V. (2020). Systematic dissection of biases in whole‐exome and whole‐genome sequencing reveals major determinants of coding sequence coverage. Scientific Reports, 10, 2057. 10.1038/s41598-020-59026-y - DOI - PMC - PubMed
    1. Begemann, A. , Acuña, M. A. , Zweier, M. , Vincent, M. , Steindl, K. , Bachmann‐Gagescu, R. , Hackenberg, A. , Abela, L. , Plecko, B. , Kroell‐Seger, J. , Baumer, A. , Yamakawa, K. , Inoue, Y. , Asadollahi, R. , Sticht, H. , Zeilhofer, H. U. , & Rauch, A. (2019). Further corroboration of distinct functional features in SCN2A variants causing intellectual disability or epileptic phenotypes. Molecular Medicine, 25, 6. 10.1186/s10020-019-0073-6 - DOI - PMC - PubMed
    1. Bramswig, N. C. , Lüdecke, H.‐J. , Hamdan, F. F. , Altmüller, J. , Beleggia, F. , Elcioglu, N. H. , Freyer, C. , Gerkes, E. H. , Demirkol, Y. K. , Knupp, K. G. , Kuechler, A. , Li, Y. , Lowenstein, D. H. , Michaud, J. L. , Park, K. , Stegmann, A. P. A. , Veenstra‐Knol, H. E. , Wieland, T. , Wollnik, B. , … Wieczorek, D. (2017). Heterozygous HNRNPU variants cause early onset epilepsy and severe intellectual disability. Human Genetics, 136(7), 821–834. 10.1007/s00439-017-1795-6 - DOI - PubMed
    1. Chintalaphani, S. R. , Pineda, S. S. , Deveson, I. W. , & Kumar, K. R. (2021). An update on the neurological short tandem repeat expansion disorders and the emergence of long‐read sequencing diagnostics. Acta Neuropathologica Communications, 9(19), 98. 10.1186/s40478-021-01201-x - DOI - PMC - PubMed
    1. Dai, P. , Zhu, X. , Pei, Y. , Chen, P. , Li, J. , Gao, Z. , Liang, Y. , & Kong, X. (2022). Evaluation of optical genome mapping for detecting chromosomal translocation in clinical cytogenetics. Molecular Genetics and Genomic Medicine, 10(6), 1–9. 10.1002/mgg3.1936 - DOI - PMC - PubMed

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