诊断基因组测序改善诊断产量:一项前性单中心研究,涉及1000名患有遗传性眼病的患者
Nicole Weisschuh1, Pascale Mazzola2, Theresia Zuleger2
1Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
Journal of medical genetics
|September 21, 2023
概括
基因组测序 (GS) 是一种可行的工具,用于诊断罕见的遗传疾病,如遗传性视网膜退化 (IRD) 和遗传性视神经病变 (ION). 这种方法有效地识别结构变异和非编码突变,改善临床实践中的诊断率.
科学领域:
- 遗传学 遗传学 是一个
- 基因组学就是基因组学.
- 罕见疾病 罕见疾病
背景情况:
- 基因组测序 (GS) 旨在弥合罕见遗传疾病的诊断差距.
- 遗传性视网膜退化 (IRD) 和遗传性视神经病变 (ION) 是重要的罕见遗传疾病.
- 评估超出外基因组测序的先进基因组分析对于改善诊断至关重要.
研究的目的:
- 评估一种可扩展的基因组分析框架,用于对IRD和ION患者的常规护理.
- 评估整个基因组测序的实用性,以诊断罕见的遗传神经病变和视网膜疾病.
- 优化生物信息学管道,用于分析结构变异和非编码区域.
主要方法:
- 在1000名连续的IRD/ION患者中进行了PCR无需的短读基因组测序.
- 在74名患者的亚组中进行了补充全血RNA测序.
- 利用并优化了一个开源生物信息学管道,用于变量调用和解释.
主要成果:
- 在57.4%的病例中获得了确定的遗传诊断.
- 在16.7%的患者中发现了具有不确定意义的变异.
- 发现结构变异 (SVs) 和非编码变化占确定的变异的12.7%.
- RNA测序有助于分类两种以前不确定的变异.
结论:
- 基因组测序在临床上是可行的,并且有效地识别罕见遗传疾病的因果变异.
- 通过检测罕见的非编码变体和精确的SVs,GS提高了诊断产量.
- 由于血液中的基因表达低,RNA测序为IRD/ION提供了有限的额外诊断价值.
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