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

Mélanie Eyries

doi:10.1038/s41431-022-01064-3

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

2022-03-11

3

OA

AI

Odile Cohen‐Haguenauer

DOI：10.1038/s41431-022-01064-3

Original

Original request for help

Save

Abstract

En 中文

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.

Keywords:

GERMLINE MUTATIONS

HEREDITARY BREAST

SUSCEPTIBILITY

GUIDELINES

ASSOCIATION

FAMILIES

PARTNER

RISK

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

Abstract

Journal

Organization