Department of Molecular and Medical Genetics, Hospices Civils de Lyon, University Hospital, 69500 Bron, France.
Unit of Prevention and Genetic Epidemiology, UMR CNRS 5558, Centre Léon Bérard, 69008 Lyon, France.
Genes (Basel). 2021 Oct 29;12(11):1736. doi: 10.3390/genes12111736.
Hereditary breast and ovarian cancer syndrome (HBOC) is an autosomal dominant cancer predisposition syndrome characterized by an increased risk of breast and ovarian cancers. Germline pathogenic variants in are found in about 7-10% of all familial breast cancers and 10% of ovarian cancers. elements are the most abundant mobile DNA element in the human genome and are known to affect the human genome by different mechanisms leading to human disease. We report here the detection, by next-generation sequencing (NGS) analysis coupled with a suitable bioinformatics pipeline, of an Yb8 element in exon 14 of the gene in a family with HBOC history first classified as BRCA-negative by Sanger sequencing and first NGS analysis. The c.4475_c.4476insYb8 mutation impacts splicing and induces the skipping of exon 14. As a result, the produced mRNA contains a premature stop, leading to the production of a short and likely non-functional protein (pAla1453Glyfs*10). Overall, our study allowed us to identify a novel pathogenic variant in and showed the importance of bioinformatics tool improvement and versioning.
遗传性乳腺癌和卵巢癌综合征（HBOC）是一种常染色体显性遗传的癌症易感性综合征，其特征是乳腺癌和卵巢癌的风险增加。在所有家族性乳腺癌中约有 7-10%和卵巢癌中约有 10%发现存在 种系致病性变异。LINE1 元件是人类基因组中最丰富的可移动 DNA 元件，已知通过不同的机制影响人类基因组，导致人类疾病。我们在此报告了通过下一代测序（NGS）分析与合适的生物信息学管道在一个具有 HBOC 病史的家族中检测到 的外显子 14 中的 Yb8 元件的情况，该家族首先通过桑格测序和首次 NGS 分析被归类为 BRCA 阴性。c.4475_c.4476insYb8 突变影响剪接并导致外显子 14 的跳跃。结果，产生的 mRNA 包含一个提前终止，导致产生一个短的且可能无功能的蛋白质（pAla1453Glyfs*10）。总的来说，我们的研究使我们能够鉴定出 中的一种新的致病性变异，并表明了改进和版本控制生物信息学工具的重要性。
