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Detection of a pathogenic Alu element insertion in PALB2 gene from targeted NGS diagnostic data

European Journal of Human Genetics volume 30, pages 1187–1190 (2022)Cite this article

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Abstract

Despite routine analysis of a large panel of genes, pathogenic variants are only detected in approximately 20% of families with hereditary breast and/or ovarian cancer. Mobile element insertions (MEI) are known to cause genetic diseases in humans, but remain challenging to detect. Retrospective analysis of targeted next-generation sequencing (NGS) data from 359 patients was performed using a dedicated MEI detection pipeline. We detected one MEI in exon 9 of the PALB2 gene in a woman with a family history of breast cancer. The pathogenic variant, c.2872_2888delins114AluL2, disrupts the PALB2 coding sequence and leads to the production of a truncated protein, p.(Gln958Valfs*38). This is the first report of a pathogenic MEI in PALB2. This study illustrates that MEI analysis may help to improve molecular diagnostic yield and can be performed from targeted NGS data used for routine diagnosis.

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Fig. 1: Mobile element insertion (MEI) in exon 9 of the PALB2 gene.

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Data availability

All additional data not provided in this article are available from the corresponding authors upon reasonable request. If you are interested in using the MEI detection pipeline, please contact pierre.delagrange@genodiag.com.

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Acknowledgements

We would like to thank Dr. Stéphanie Baert-Desurmont for providing the MSH2 Alu insertion fastq files.

Author contributions

FC supervised the study and contributed to analyzing data, interpreting result, and writing the manuscript. ME designed the experiments and contributed to analyzing data, interpreting result, and writing the manuscript. OA, PDLG conceived and realized bioinformatic analyses and contributed to writing the manuscript. GL performed technical experiments. NB, EG, AP contributed to analyzing data and interpreting results. CD, OC-H collected and analyzed clinical data. All authors reviewed the manuscript.

Funding

No specific funding support this study.

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Authors and Affiliations

  1. Sorbonne Université, Département de génétique, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, F-75013, Paris, France

    Mélanie Eyries, Gaelle Legrand, Noémie Basset, Erell Guillerm, Alexandre Perrier & Florence Coulet

  2. GenoDiag, Paris, France

    Olivier Ariste & Pierre de la Grange

  3. Hôpital Saint-Louis–Lariboisière–Fernand-Widal, Service d’oncologie médicale Assistance Publique-Hôpitaux de Paris, F-75010, Paris, France

    Caroline Duros & Odile Cohen-Haguenauer

Authors
  1. Mélanie Eyries
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  2. Olivier Ariste
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  3. Gaelle Legrand
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  4. Noémie Basset
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  8. Odile Cohen-Haguenauer
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Corresponding author

Correspondence to Mélanie Eyries.

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The authors declare no competing interests.

Ethical approval

All patients gave their informed consent for genetic research, which was approved by the “Comité de Protection des Personnes Ile de France-VI”, decision ID RCB2007-AO1347-46.

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Eyries, M., Ariste, O., Legrand, G. et al. Detection of a pathogenic Alu element insertion in PALB2 gene from targeted NGS diagnostic data. Eur J Hum Genet 30, 1187–1190 (2022). https://doi.org/10.1038/s41431-022-01064-3

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