UCL Great Ormond Street Institute of Child Health, London, UK.
UCL Great Ormond Street Institute of Child Health, London, UK
Clin Med (Lond). 2019 Jan;19(1):30-36. doi: 10.7861/clinmedicine.19-1-30.
Inherited metabolic disorders (IMDs) are debilitating inherited diseases, with phenotypic, biochemical and genetic heterogeneity, frequently leading to prolonged diagnostic odysseys. Mitochondrial disorders represent one of the most severe classes of IMDs, wherein defects in >350 genes lead to multi-system disease. Diagnostic rates have improved considerably following the adoption of next-generation sequencing (NGS) technologies, but are still far from perfect. Phenomic annotation is an emerging concept which is being utilised to enhance interpretation of NGS results. To test whether phenomic correlations have utility in mitochondrial disease and IMDs, we created a gene-to-phenotype interaction network with searchable elements, for Leigh syndrome, a frequently observed paediatric mitochondrial disorder. The Leigh Map comprises data on 92 genes and 275 phenotypes standardised in human phenotype ontology terms, with 80% predictive accuracy. This commentary highlights the usefulness of the Leigh Map and similar resources and the challenges associated with integrating phenomic technologies into clinical practice.
遗传性代谢紊乱（IMDs）是一种使人衰弱的遗传性疾病，具有表型、生化和遗传异质性，常常导致冗长的诊断探索过程。线粒体疾病是 IMDs 中最严重的一类，其中 >350 种基因的缺陷会导致多系统疾病。在采用下一代测序（NGS）技术后，诊断率有了显著提高，但仍远未完善。表型注释是一个新兴概念，正在被用于增强对 NGS 结果的解读。为了测试表型相关性在线粒体疾病和 IMDs 中的应用价值，我们创建了一个 Leigh 综合征的基因-表型相互作用网络， Leigh 综合征是一种常见的儿科线粒体疾病。 Leigh 图谱包含了 92 个基因和 275 种表型的数据，这些数据以人类表型本体论术语标准化，具有 80%的预测准确性。这篇评论强调了 Leigh 图谱和类似资源的有用性，以及将表型技术整合到临床实践中所面临的挑战。
