Urine contains extracellular RNA (exRNA) markers of urogenital cancers. However, the capacity of genetic material in urine to identify systemic diseases is unknown. Here we describe exRNA splice products in human urine as a source of biomarkers for the two most common forms of muscular dystrophies, myotonic dystrophy (DM) and Duchenne muscular dystrophy (DMD). Using a training set, RT-PCR, droplet digital PCR, and principal component regression, we identify ten transcripts that are spliced differently in urine exRNA from patients with DM type 1 (DM1) as compared to unaffected or disease controls, form a composite biomarker, and develop a predictive model that is 100% accurate in our independent validation set. Urine also contains mutation-specific DMD mRNAs that confirm exon-skipping activity of the antisense oligonucleotide drug eteplirsen. Our results establish that urine mRNA splice variants can be used to monitor systemic diseases with minimal or no clinical effect on the urinary tract.

中文翻译：

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人类尿液中细胞外 mRNA 的分析揭示了肌营养不良症的剪接变异生物标志物。

尿液中含有泌尿生殖系统癌症的细胞外 RNA (exRNA) 标志物。然而，尿液中的遗传物质识别全身性疾病的能力尚不清楚。在这里，我们将人类尿液中的 exRNA 剪接产物描述为两种最常见的肌营养不良症、强直性肌营养不良症 (DM) 和杜氏肌营养不良症 (DMD) 的生物标志物来源。使用训练集、RT-PCR、液滴数字 PCR 和主成分回归，我们从 1 型 DM (DM1) 患者的尿液 exRNA 中鉴定出与未受影响或疾病对照相比剪接不同的十个转录物，形成复合生物标志物，并在我们的独立验证集中开发一个 100% 准确的预测模型。尿液中还含有突变特异性 DMD mRNA，可证实反义寡核苷酸药物 eteplirsen 的外显子跳跃活性。