一个都不能少!诊断罕见病的创新技术应用专家建议。

Leaving no patient behind! Expert recommendation in the use of innovative technologies for diagnosing rare diseases.

机构信息

Departments of Pediatrics and Human Genetics, Emma Center for Personalized Medicine, Amsterdam Gastro-Enterology Endocrinology Metabolism, Amsterdam University Medical Centers, Amsterdam, The Netherlands.

Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, USA.

出版信息

Orphanet J Rare Dis. 2024 Sep 27;19(1):357. doi: 10.1186/s13023-024-03361-0.

Abstract

Genetic diagnosis plays a crucial role in rare diseases, particularly with the increasing availability of emerging and accessible treatments. The International Rare Diseases Research Consortium (IRDiRC) has set its primary goal as: "Ensuring that all patients who present with a suspected rare disease receive a diagnosis within one year if their disorder is documented in the medical literature". Despite significant advances in genomic sequencing technologies, more than half of the patients with suspected Mendelian disorders remain undiagnosed. In response, IRDiRC proposes the establishment of "a globally coordinated diagnostic and research pipeline". To help facilitate this, IRDiRC formed the Task Force on Integrating New Technologies for Rare Disease Diagnosis. This multi-stakeholder Task Force aims to provide an overview of the current state of innovative diagnostic technologies for clinicians and researchers, focusing on the patient's diagnostic journey. Herein, we provide an overview of a broad spectrum of emerging diagnostic technologies involving genomics, epigenomics and multi-omics, functional testing and model systems, data sharing, bioinformatics, and Artificial Intelligence (AI), highlighting their advantages, limitations, and the current state of clinical adaption. We provide expert recommendations outlining the stepwise application of these innovative technologies in the diagnostic pathways while considering global differences in accessibility. The importance of FAIR (Findability, Accessibility, Interoperability, and Reusability) and CARE (Collective benefit, Authority to control, Responsibility, and Ethics) data management is emphasized, along with the need for enhanced and continuing education in medical genomics. We provide a perspective on future technological developments in genome diagnostics and their integration into clinical practice. Lastly, we summarize the challenges related to genomic diversity and accessibility, highlighting the significance of innovative diagnostic technologies, global collaboration, and equitable access to diagnosis and treatment for people living with rare disease.

摘要

遗传诊断在罕见病中起着至关重要的作用,特别是随着新兴和可及治疗方法的不断增加。国际罕见病研究联合会(IRDiRC)将其首要目标设定为:“确保所有疑似罕见病患者,如果其疾病在医学文献中有记录,在一年内得到诊断”。尽管基因组测序技术取得了重大进展,但仍有一半以上疑似孟德尔疾病的患者未得到诊断。为此,IRDiRC 提出建立“一个全球协调的诊断和研究管道”。为了帮助实现这一目标,IRDiRC 成立了罕见病诊断新技术整合工作组。这个多利益相关方的工作组旨在为临床医生和研究人员提供创新诊断技术的现状概述,重点关注患者的诊断过程。在此,我们概述了涉及基因组学、表观基因组学和多组学、功能测试和模型系统、数据共享、生物信息学和人工智能 (AI) 的新兴诊断技术的广泛领域,强调了它们的优势、局限性以及当前的临床适应性。我们提供了专家建议,概述了在考虑全球可及性差异的情况下,这些创新技术在诊断途径中的逐步应用。强调了 FAIR(可发现性、可访问性、互操作性和可重用性)和 CARE(集体利益、控制权限、责任和道德)数据管理的重要性,以及医学基因组学方面的强化和持续教育的必要性。我们提供了对基因组诊断未来技术发展及其纳入临床实践的看法。最后,我们总结了与基因组多样性和可及性相关的挑战,强调了创新诊断技术、全球合作以及为罕见病患者提供公平的诊断和治疗机会的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60a4/11438178/de7d5f16aeb4/13023_2024_3361_Fig1_HTML.jpg

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