基因组测序在具有神经发育表型的外体阴性儿科患者中的实用性
Tomoki T Nomakuchi1, Eden Y Teferedegn1, Dong Li1
1Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
American journal of medical genetics. Part A
|July 20, 2024
概括
基因组测序 (GS) 对神经发育障碍 (NDD) 的外体组测序 (ES) 提供了全面的诊断优势. 在9例儿科NDD病例中,GS确定了因果变异,其中4例被之前的ES遗漏.
科学领域:
- 基因组学就是基因组学.
- 儿科神经学 儿科神经学
- 罕见疾病 罕见疾病
背景情况:
- 外体序列测序 (ES) 是诊断来源不明的神经发育障碍 (NDD) 的主要工具.
- 基因组测序 (GS) 提供了更广泛的变异检测能力,包括结构变异,复制号和非编码变异,但由于成本和分析复杂性,使用率较低.
- 许多NDD病例在ES后仍然未被诊断,需要先进的基因组方法.
研究的目的:
- 评估基因组测序 (GS) 在儿科神经发育障碍 (NDD) 病例中的诊断实用性,先前未诊断出外基因组测序 (ES).
- 为了确定GS发现的特定变异类型和基因,ES错过了它们.
主要方法:
- 在2017年至2022年间通过GS诊断的9例儿科NDD病例的回顾性分析,在最初的非诊断ES之后.
- 通过GS检测到的变异类型的审查,包括结构变异,非编码变异和新建立疾病关联的基因变异.
- 将GS和ES之间的诊断产量进行比较,并指出GS唯一识别的变异.
主要成果:
- 在ES之前评估的9个儿科NDD病例中,GS成功诊断出致病变体.
- 具体的诊断成功包括识别MAPK8IP3和CHD3 (新描述的基因-疾病关系) 的变异,中等大小的删除,非编码变异 (SNORD118,RNU7-1),促进器变异 (GJB1) 和覆盖较差的异区域 (BCAP31) 的变异.
- 四个诊断完全归因于GS,突出了ES的局限性和GS再分析的好处.
结论:
- 基因组测序是诊断儿科神经发育障碍的强大工具,特别是当外基因组测序没有诊断时.
- GS检测到更广泛的致病变体,包括结构,非编码和促进区域变体,ES错过了.
- 在非诊断性ES之后实施GS显著增加了复杂NDD病例的诊断产量.
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