摘要
约25-50万美国人,3000万个欧洲人,8%的澳大利亚人口有一种罕见的疾病。因此,罕见的疾病是临床医生普遍存在的问题,而且由于建立一个特定的诊断困难,在世界范围内造成了巨大的医疗费用。在这篇文章中,我们回顾了我们的里程碑在罕见疾病的认识以来出现的新一代测序(NGS)技术,分析了这些进展影响的研究和诊断。这篇评论的前半部分介绍了如何使用改变了诊断流程和提供了一个前所未有的,发现新的疾病相关基因的简单方法。我们特别关注代谢和神经发育障碍。NGS使廉价和快速基因诊断,突出了马赛克和de novo突变的相关性,揭示了大部分基因的广泛的表型谱,发现双继承或多个罕见病存在于同一患者,和有前途的新的治疗方法铺平了道路。在第二部分的检讨,看看我们的局限和挑战的农工商,包括变量因果关系的确定,在编码区和非编码区变异的损失,和体细胞嵌合体的变异和表观遗传突变的检测,并讨论如何将这些在不久的将来能克服。
关键词: 下一代测序,罕见疾病,诊断,研究,遗传,基因组,外显子。
Current Medicinal Chemistry
Title:NGS Technologies as a Turning Point in Rare Disease Research , Diagnosis and Treatment
Volume: 25 Issue: 3
关键词: 下一代测序,罕见疾病,诊断,研究,遗传,基因组,外显子。
摘要: Approximately 25-50 million Americans, 30 million Europeans, and 8% of the Australian population have a rare disease. Rare diseases are thus a common problem for clinicians and account for enormous healthcare costs worldwide due to the difficulty of establishing a specific diagnosis. In this article, we review the milestones achieved in our understanding of rare diseases since the emergence of next-generation sequencing (NGS) technologies and analyze how these advances have influenced research and diagnosis. The first half of this review describes how NGS has changed diagnostic workflows and provided an unprecedented, simple way of discovering novel disease-associated genes. We focus particularly on metabolic and neurodevelopmental disorders. NGS has enabled cheap and rapid genetic diagnosis, highlighted the relevance of mosaic and de novo mutations, brought to light the wide phenotypic spectrum of most genes, detected digenic inheritance or the presence of more than one rare disease in the same patient, and paved the way for promising new therapies. In the second part of the review, we look at the limitations and challenges of NGS, including determination of variant causality, the loss of variants in coding and non-coding regions, and the detection of somatic mosaicism variants and epigenetic mutations, and discuss how these can be overcome in the near future.
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NGS Technologies as a Turning Point in Rare Disease Research , Diagnosis and Treatment, Current Medicinal Chemistry 2018; 25 (3) . https://dx.doi.org/10.2174/0929867324666170718101946
DOI https://dx.doi.org/10.2174/0929867324666170718101946 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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