Intron retention induced by microsatellite expansions as a disease biomarker

Łukasz J. Sznajder, James D. Thomas, Ellie M. Carrell, Tammy Reid, Karen N. McFarland, John D. Cleary, Ruan Oliveira, Curtis A. Nutter, Kirti Bhatt, Krzysztof Sobczak, Tetsuo Ashizawa, Charles A. Thornton, Laura P.W. Ranum, Maurice S. Swanson

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


Expansions of simple sequence repeats, or microsatellites, have been linked to ∼30 neurological–neuromuscular diseases. While these expansions occur in coding and noncoding regions, microsatellite sequence and repeat length diversity is more prominent in introns with eight different trinucleotide to hexanucleotide repeats, causing hereditary diseases such as myotonic dystrophy type 2 (DM2), Fuchs endothelial corneal dystrophy (FECD), and C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). Here, we test the hypothesis that these GC-rich intronic microsatellite expansions selectively trigger host intron retention (IR). Using DM2, FECD, and C9-ALS/FTD as examples, we demonstrate that retention is readily detectable in affected tissues and peripheral blood lymphocytes and conclude that IR screening constitutes a rapid and inexpensive biomarker for intronic repeat expansion disease.

Original languageEnglish (US)
Pages (from-to)4234-4239
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number16
StatePublished - Apr 17 2018


  • Amyotrophic lateral sclerosis
  • RNA splicing
  • intron retention
  • microsatellite
  • myotonic dystrophy

ASJC Scopus subject areas

  • General


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