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利用基因组生物库来提高病遗传测试结果
medRxiv : the preprint server for health sciences
|November 26, 2025
概括
慢性病 (CKD) 的基因检测发现了34%的诊断产量,并导致大多数积极病例的管理变化. 一种多学科的方法成功地重新分类了不确定的遗传变异,提高了病患者的诊断准确度.
科学领域:
- 腎病學與遺傳學 的相關專題
- 基因组医学是基因组医学.
- 临床诊断 临床诊断 临床诊断
背景情况:
- 慢性病 (CKD) 影响全球9.1%,带来显著的发病率和死亡率.
- 对CKD的遗传检测具有高达10%的诊断收益率,但通常会导致具有不确定的意义的变异 (VUS).
- 对遗传检测结果的有效解释对于患者管理至关重要.
研究的目的:
- 报告228名患有病表型的患者队列中的遗传检测结果.
- 评估诊断产量,管理变化和VUS解决策略.
- 评估多学科方法对遗传检测临床实用性的影响.
主要方法:
- 对228名接受病遗传检测的患者 (2020-2023) 的回顾性分析.
- 涉及科和遗传咨询师的多学科审查,用于VUS解决方案.
- 整合遗传数据库,专家小组,功能测试和大规模的外体序列数据 (Geisinger MyCode DiscovEHR) 与电子健康记录相关.
主要成果:
- 在34%的患者中发现了积极的 (致病性/可能致病性) 遗传结果,52%的患者只有VUS;14%的患者有负面结果.
- 报告中平均每位患者的VUS为4.0;多学科审查导致10个VUS重新归类为可能致病的,并将10个VUS降级为可能良性的.
- 基因检测导致了 88.5% 的阳性病例的直接管理变化,并且在 37.7% 的患者中产生了家族影响.
结论:
- 综合生物库数据,外基因组测序,EHR,功能测试和实验室合作的多学科方法增强了VUS重新分类.
- 这种方法最大限度地提高了对病遗传检测的临床实用性,影响了诊断,预后和管理.
- 有效的VUS解释是释放脏病学遗传诊断的全部潜力的关键.
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