Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, NC, USA.
University of Utah and ARUP Laboratories, Salt Lake City, UT, USA.
Mol Genet Metab. 2019 Sep-Oct;128(1-2):122-128. doi: 10.1016/j.ymgme.2019.07.008. Epub 2019 Jul 18.
Newborn screening is an incredibly useful tool for the early identification of many metabolic disorders, including fatty acid oxidation (FAO) disorders. In many cases, molecular tests are necessary to reach a final diagnosis, highlighting the need for a thorough evaluation of genes implicated in FAO disorders. Using the ClinGen (Clinical Genome Resource) clinical validity framework, thirty genes were analyzed for the strength of evidence supporting their association with FAO disorders. Evidence was gathered from the literature by biocurators and presented to disease experts for review in order to assign a clinical validity classification of Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Reported Evidence. Of the gene-disease relationships evaluated, 22/30 were classified as Definitive, three as Moderate, one as Limited, three as No Reported Evidence and one as Disputed. Gene-disease relationships with a Limited, Disputed, and No Reported Evidence were found on two, six, and up to four panels out of 30 FAO disorder-specific panels, respectively, in the National Institute of Health Genetic Testing Registry, while over 70% of the genes on panels are definitively associated with an FAO disorder. These results highlight the need to systematically assess the clinical relevance of genes implicated in fatty acid oxidation disorders in order to improve the interpretation of genetic testing results and diagnosis of patients with these disorders.
新生儿筛查是一种非常有用的工具，可以早期发现许多代谢紊乱，包括脂肪酸氧化（FAO）紊乱。在许多情况下，需要进行分子测试才能得出最终诊断，这突出表明需要对与 FAO 紊乱相关的基因进行彻底评估。使用 ClinGen（临床基因组资源）临床有效性框架，对 30 个基因进行了分析，以确定支持它们与 FAO 紊乱相关的证据强度。生物信息学专家从文献中收集证据，并提交给疾病专家审查，以确定临床有效性分类为明确、强烈、中等、有限、有争议、反驳或无报告证据。在所评估的基因-疾病关系中，22/30 被归类为明确，3 个为中等，1 个为有限，3 个为无报告证据，1 个为有争议。在国家卫生研究院遗传检测登记处的 30 个 FAO 紊乱特异性面板中，分别有 2 个、6 个和多达 4 个面板的基因-疾病关系为有限、有争议和无报告证据，而超过 70%的面板基因与 FAO 紊乱明确相关。这些结果强调需要系统评估与脂肪酸氧化紊乱相关的基因的临床相关性，以改善对这些基因的遗传检测结果的解释和对这些疾病患者的诊断。
