通过HiFi长时间读取的基因组测序,揭开未被诊断的罕见疾病病例
Wouter Steyaert1, Lydia Sagath1, German Demidov2
1Radboud University Medical Center, Department of Human Genetics, Research Institute for Medical Innovation, 6500 HB Nijmegen, Netherlands.
Genome research
|March 26, 2025
概括
在之前缺乏诊断的11.8%的罕见疾病家族中,HiFi长时间读取测序确定了遗传原因. 这种先进的基因组方法为诊断罕见遗传疾病提供了新的希望.
科学领域:
- 基因组学就是基因组学.
- 罕见疾病 罕见疾病
- 遗传医学是一种遗传医学.
背景情况:
- 罕见疾病 (RD) 通常会带来诊断挑战,许多家庭缺乏分子诊断.
- 之前的基因测试未能在很大一部分RD病例中确定致病变体.
研究的目的:
- 利用HiFi长读测序 (LRS) 来识别未被诊断的罕见疾病家族中的遗传变异.
- 评估LRS在解决以前未解决的罕见疾病病例中的诊断收益率.
主要方法:
- 使用10倍覆盖的HiFi LRS检测结构变体 (SV),单核酸变体 (SNV),插入删除 (indels) 和短串重复 (STR) 扩展.
- 分析了来自114个遗传未诊断的RD家族的293个人,包括那些患有"无法解决"综合征和罕见的神经/神经肌肉/疾病的人.
主要成果:
- 通过de novo和罕见的遗传SNVs,indels,SVs和STR扩展实现了12项新的遗传诊断.
- 在另外五个家族中确定了引起疾病的候选变异,包括基因融合和删除.
- 在"不可解决"综合征中没有发现共同的遗传原因,但在以前未解决的家庭中,在11.8%的患者中发现了可能引起疾病的变体,在5.4%的患者中确定了可能引起疾病的变体.
结论:
- 长时间读取的HiFi基因组测序证明了诊断罕见疾病的显著附加值.
- 这项技术可以发现各种遗传变异类型,包括复杂的结构变异和重复扩张,其他方法无法发现.
- 该研究强调了LRS在挑战性罕见疾病病例中提高诊断率的潜力.
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