The use of precision diagnostics for monogenic diabetes: a systematic review and expert opinion.
The use of precision diagnostics for monogenic diabetes: a systematic review and expert opinion.
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DOI：
10.1038/s43856-023-00369-8
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发表时间：
2023-10-05
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影响因子：
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通讯作者：
Gloyn, Anna L
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作者：
Murphy, Rinki;Colclough, Kevin;Pollin, Toni I;Ikle, Jennifer M;Svalastoga, Pernille;Maloney, Kristin A;Saint-Martin, Cecile;Molnes, Janne;Misra, Shivani;Aukrust, Ingvild;de Franco, Elisa;Flanagan, Sarah E;Njolstad, Pal R;Billings, Liana K;Owen, Katharine R;Gloyn, Anna L
单基因糖尿病为精准医疗提供了机会，但诊断不足。本综述系统地评估了（1）单基因糖尿病基因检测的临床标准和（2）方法的证据，总结了（3）将基因或（4）变异视为单基因糖尿病病因的资源，为（5）报告结果提供了专家建议;并回顾了（6）单基因糖尿病诊断后的下一步措施和（7）精准医学领域的挑战。使用入选/排除标准检索Pubmed和Embase数据库（1990-2022年），检索对至少100名先证者的一个或多个单基因糖尿病基因进行测序的研究（问题1），评价诊断单基因糖尿病的非过时基因检测方法（问题2）。使用修订后的QUADAS-2工具评估偏倚风险。对问题3-5概述了现有准则，对问题6-7审查了研究报告，并以专家建议作为补充。结果总结在表格中，并为临床实践提供了知情建议。问题1、2、6和7分别包含100项、32项、36项和14项研究。在此基础上，提供了四个关于谁来测试和五个关于如何测试单基因糖尿病的建议。总结了变异治疗和基因-疾病有效性治疗的现有指南。推荐使用基因名称报告，作为术语MODY的替代。重点介绍了基因诊断后的关键步骤以及我们目前知识中的主要差距。我们提供了一个综合的目前的证据和专家意见，如何使用精确的诊断，以确定个人与单基因糖尿病。一些糖尿病类型，称为单基因糖尿病，是由单个基因的变化引起的。重要的是要知道谁有这种糖尿病，因为治疗可以不同于其他类型的糖尿病。对于特定类型的人，有些治疗方法也比其他治疗方法效果更好，有些人可以从注射胰岛素改为服用片剂。此外，可以为亲属提供测试，看看他们是否有风险。诊断单基因糖尿病需要进行基因检测，但价格昂贵，因此不可能对每个糖尿病患者进行检测。我们评估了已发表的关于谁应该接受检测以及使用什么检测的研究。基于此，我们为医生和医疗保健提供者提供如何实施单基因糖尿病基因检测的建议。Murphy、Kevin、Pollin等人对用于选择糖尿病个体进行基因检测的标准的证据以及单基因糖尿病相关基因变异检测的最佳方法的证据进行了系统性综述。根据调查结果，作者提出了建议，并强调了该领域的挑战。
Monogenic diabetes presents opportunities for precision medicine but is underdiagnosed. This review systematically assessed the evidence for (1) clinical criteria and (2) methods for genetic testing for monogenic diabetes, summarized resources for (3) considering a gene or (4) variant as causal for monogenic diabetes, provided expert recommendations for (5) reporting of results; and reviewed (6) next steps after monogenic diabetes diagnosis and (7) challenges in precision medicine field. Pubmed and Embase databases were searched (1990-2022) using inclusion/exclusion criteria for studies that sequenced one or more monogenic diabetes genes in at least 100 probands (Question 1), evaluated a non-obsolete genetic testing method to diagnose monogenic diabetes (Question 2). The risk of bias was assessed using the revised QUADAS-2 tool. Existing guidelines were summarized for questions 3-5, and review of studies for questions 6-7, supplemented by expert recommendations. Results were summarized in tables and informed recommendations for clinical practice. There are 100, 32, 36, and 14 studies included for questions 1, 2, 6, and 7 respectively. On this basis, four recommendations for who to test and five on how to test for monogenic diabetes are provided. Existing guidelines for variant curation and gene-disease validity curation are summarized. Reporting by gene names is recommended as an alternative to the term MODY. Key steps after making a genetic diagnosis and major gaps in our current knowledge are highlighted. We provide a synthesis of current evidence and expert opinion on how to use precision diagnostics to identify individuals with monogenic diabetes. Some diabetes types, called monogenic diabetes, are caused by changes in a single gene. It is important to know who has this kind of diabetes because treatment can differ from that of other types of diabetes. Some treatments also work better than others for specific types, and some people can for example change from insulin injections to tablets. In addition, relatives can be offered a test to see if they are at risk. Genetic testing is needed to diagnose monogenic diabetes but is expensive, so it’s not possible to test every person with diabetes for it. We evaluated published research on who should be tested and what test to use. Based on this, we provide recommendations for doctors and health care providers on how to implement genetic testing for monogenic diabetes. Murphy, Kevin, Pollin et al. perform a systematic review of the evidence on the criteria used to select individuals with diabetes for genetic testing and of the evidence for the optimal methods for variant detection in genes involved in monogenic diabetes. Based on the findings the authors make recommendations and highlight challenges for the field.