PDF(Pubmed)
Abstract：
Background: Next-generation sequencing-based genetic testing represents a great opportunity to identify hereditary predispositions to specific pathological conditions and to promptly implement health surveillance or therapeutic protocols in case of disease. The term secondary finding refers to the active search for causative variants in genes associated with medically actionable conditions. Methods: We evaluated 59 medically actionable ACMG genes using a targeted in silico analysis of clinical exome sequencing performed in 383 consecutive individuals referred to our Medical Genetics Unit. A three-tier classification system of SFs for assessing their clinical impact and supporting a decision-making process for reporting was established. Results: We identified SFs with high/moderate evidence of pathogenicity in 7.0% (27/383) of analyzed subjects. Among these, 12/27 (44.4%) were carriers of a high-risk recessive disease allele. The most represented disease domains were cancer predisposition (33.3%), cardiac disorders (16.7%), and familial hypercholesterolemia (12.5%). Conclusion: Although still debated, ensuring during NGS-based genetic testing an opportunistic screening might be valuable for personal and familial early management and surveillance of medically actionable disorders, the individual\'s reproductive choices, and the prevalence assessment of underestimated hereditary genetic diseases.
摘要：
背景：下一代基于测序的基因检测代表了一个很好的机会，可以识别特定病理状况的遗传易感性，并在疾病发生时及时实施健康监测或治疗方案。术语次要发现是指主动搜索与医学上可操作的病症相关的基因中的致病变体。方法：我们使用对383名连续个体进行的临床外显子组测序的靶向计算机分析，评估了59个医学上可操作的ACMG基因，这些个体被转介给我们的医学遗传学部门。建立了SF的三层分类系统，用于评估其临床影响并支持报告决策过程。结果：我们在7.0％（27/383）的分析受试者中鉴定出具有高/中等致病性证据的SF。其中,12/27（44.4％）是高风险隐性疾病等位基因的携带者。最具代表性的疾病领域是癌症易感性(33.3%)，心脏疾病（16.7%），和家族性高胆固醇血症（12.5％）。结论：尽管仍在争论中，在基于NGS的基因检测中，确保机会性筛查对于个人和家庭早期管理和监测医学上可行的疾病可能是有价值的，个人的生殖选择，以及低估的遗传性遗传病的患病率评估。
