Hereditary Cancer Laboratory, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.
Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain.
Genes (Basel). 2023 Feb 15;14(2):502. doi: 10.3390/genes14020502.
Hereditary breast and ovarian cancer syndrome (HBOC) is a clinical entity characterized by an increased risk of developing breast and ovarian cancer. The genetic diagnosis is based on the identification of heterozygous germinal variants in HBOC susceptibility genes. However, it has recently been described that constitutional mosaic variants can contribute to the aetiology of HBOC. In constitutional mosaicism, individuals have at least two genotypically distinct populations of cells that arise from an early post-zygote event. The mutational event occurs early enough in development to affect several tissues. It is detected in germinal genetic studies as low variant allele frequency (VAF) variants (<30%) that are generally overlooked during the prioritization process. Constitutional mosaic variants can affect both somatic and germinal cells, and thus can be passed to the offspring and have important consequences for genetic counselling. In this work, we report the c.9648+1G>A mosaic variant in the gene and propose a diagnostic algorithm to deal with potential mosaic findings identified by Next Generation Sequencing (NGS).
遗传性乳腺癌和卵巢癌综合征 (HBOC) 是一种临床实体，其特征是患乳腺癌和卵巢癌的风险增加。基因诊断基于在 HBOC 易感性基因中发现杂合性胚系变异。然而，最近已经描述了组成性嵌合变体可能导致 HBOC 的发病机制。在组成性嵌合中，个体具有至少两种来自早期合子后事件的基因型不同的细胞群体。突变事件发生在发育过程中足够早，以至于影响到几个组织。在生殖遗传研究中，它被检测为低变异等位基因频率 (VAF) 变体(<30%)，这些变体在优先级处理过程中通常被忽略。组成性嵌合变体可以影响体细胞和生殖细胞，因此可以传递给后代，并对遗传咨询产生重要影响。在这项工作中，我们报告了基因中的 c.9648+1G>A 嵌合变体，并提出了一种诊断算法来处理下一代测序 (NGS) 识别的潜在嵌合发现。
