案例报告:CF查中的陷 - 向变异分析可能导致误导性结果和治疗建议
Maike Karnstedt1, Simone Ahting1, Sophie Behrendt1
1Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.
Frontiers in genetics
|December 16, 2025
概括
新生儿查囊性纤维化 (CF) 可能会错过复杂的CFTR基因变异. 全面的基因分析对于有效的CFTR调节器疗法和个性化治疗至关重要,特别是当反应是意想不到的.
科学领域:
- 医学遗传学 医学遗传学
- 肺部病理学 肺部病理学
- 药物基因组学 药物基因组学
背景情况:
- 德国的囊性纤维化 (CF) 诊断依赖于使用IRT/PAP和常见CFTR基因变异检测的新生儿查 (NS).
- 目前的方法有效地识别频繁的突变,但可能会错过影响CF表型和治疗结果的复杂等位基因.
研究的目的:
- 突出标准基因查在CF诊断中的局限性.
- 强调全面基因分析对优化CFTR调节器治疗的重要性.
主要方法:
- 一个儿科CF患者的病例报告通过NS.通过诊断.
- 最初的基因检测发现了同卵性F508del.
- 下一代测序 (NGS) 面板的重新测序揭示了另外一个未被检测到的异质合体致病变体.
主要成果:
- 患者最初对高汗液化物水平的Orkambi治疗表现不佳.
- NGS发现了一种错过的异质合生病原体变种.
- 切换到elexacaftor/tezacaftor/ivacaftor (ETI) 导致汗水化物水平显著改善.
结论:
- 标准CF遗传查可能无法检测复杂的等位基因,导致误诊和不理想的治疗.
- 对于那些对CFTR调节器治疗有意想不到的反应的患者,全面的基因分析是必不可少的.
- 建议进行重新测序,以指导CF护理中的精准医学方法.
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