N8-acetylspermidine as a potential plasma biomarker for Snyder-Robinson syndrome identified by clinical metabolomics
N8-acetylspermidine as a potential plasma biomarker for Snyder-Robinson syndrome identified by clinical metabolomics
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DOI：
10.1007/s10545-015-9876-y
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发表时间：
2016-01-01
影响因子：
4.2
通讯作者：
Plecko, Barbara
中科院分区：
文献类型：
--
作者：
Abela, Lucia;Simmons, Luke;Plecko, Barbara
临床代谢组学已成为研究健康和疾病中人类代谢的强大工具。非目标代谢谱的比较统计分析可以揭示疾病中代谢物水平的扰动，从而有可能识别新的生物标志物。在这里，我们对患有病因不明的癫痫性脑病的双胞胎男孩应用了同步遗传代谢组学方法。临床外显子组测序发现精胺合成酶基因 (SMS) 中存在一种新的错义突变，该突变会导致斯奈德-罗宾逊综合征 (SRS)。非靶向血浆代谢组分析显示，N-8-乙酰亚精胺（精胺生物合成的前体衍生物）水平显着升高，可作为 SRS 的潜在新型血浆生物标志物。这一结果在第三位经基因证实的 SRS 患者身上得到了验证。这项研究说明了代谢组学作为一种转化技术在功能和临床水平上支持外显子组数据的潜力。
Clinical metabolomics has emerged as a powerful tool to study human metabolism in health and disease. Comparative statistical analysis of untargeted metabolic profiles can reveal perturbations of metabolite levels in diseases and thus has the potential to identify novel biomarkers. Here we have applied a simultaneous genetic-metabolomic approach in twin boys with epileptic encephalopathy of unclear etiology. Clinical exome sequencing identified a novel missense mutation in the spermine synthase gene (SMS) that causes Snyder-Robinson syndrome (SRS). Untargeted plasma metabolome analysis revealed significantly elevated levels of N-8-acetylspermidine, a precursor derivative of spermine biosynthesis, as a potential novel plasma biomarker for SRS. This result was verified in a third patient with genetically confirmed SRS. This study illustrates the potential of metabolomics as a translational technique to support exome data on a functional and clinical level.