Analysis of extracellular mRNA in human urine reveals splice variant biomarkers of muscular dystrophies View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Layal Antoury, Ningyan Hu, Leonora Balaj, Sudeshna Das, Sofia Georghiou, Basil Darras, Tim Clark, Xandra O. Breakefield, Thurman M. Wheeler

ABSTRACT

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. More... »

PAGES

3906

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-018-06206-0

    DOI

    http://dx.doi.org/10.1038/s41467-018-06206-0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1107107975

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30254196


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