Stark Zornitza, Byrne Alicia B, Sampson Matthew G, Lennon Rachel, Mallett Andrew J
ClinGen, Boston, MA, USA.
Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
Nat Rev Nephrol. 2025 Feb;21(2):115-126. doi: 10.1038/s41581-024-00900-7. Epub 2024 Oct 23.
The use of next-generation sequencing technologies such as exome and genome sequencing in research and clinical care has transformed our understanding of the molecular architecture of genetic kidney diseases. Although the capability to identify and rigorously assess genetic variants and their relationship to disease has advanced considerably in the past decade, the curation of clinically relevant relationships between genes and specific phenotypes has received less attention, despite it underpinning accurate interpretation of genomic tests. Here, we discuss the need to accurately define gene-disease relationships in nephrology and provide a framework for appraising genetic and experimental evidence critically. We describe existing international programmes that provide expert curation of gene-disease relationships and discuss sources of discrepancy as well as efforts at harmonization. Further, we highlight the need for alignment of disease and phenotype terminology to ensure robust and reproducible curation of knowledge. These collective efforts to support evidence-based translation of genomic sequencing into practice across clinical, diagnostic and research settings are crucial for delivering the promise of precision medicine in nephrology, providing more patients with timely diagnoses, accurate prognostic information and access to targeted treatments.
在研究和临床医疗中使用外显子组测序和基因组测序等新一代测序技术，已经改变了我们对遗传性肾脏疾病分子结构的理解。尽管在过去十年中，识别和严格评估基因变异及其与疾病关系的能力有了显著提高，但基因与特定表型之间临床相关关系的整理却较少受到关注，尽管这是基因组检测准确解释的基础。在此，我们讨论了在肾脏病学中准确定义基因-疾病关系的必要性，并提供了一个批判性评估遗传和实验证据的框架。我们描述了现有的提供基因-疾病关系专家整理的国际项目，并讨论了差异来源以及协调工作。此外，我们强调了疾病和表型术语一致性的必要性，以确保知识的可靠和可重复整理。这些支持将基因组测序基于证据转化为临床、诊断和研究环境实践的集体努力，对于实现肾脏病学精准医学的前景、为更多患者提供及时诊断、准确的预后信息和靶向治疗途径至关重要。
