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

Melanie EyriesOlivier AristeGaelle LegrandNoémie BassetErell GuillermAlexandre PerrierCaroline DurosOdile Cohen-HaguenauerPierre de la GrangeFlorence Coulet
Published in: European journal of human genetics : EJHG (2022)
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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