Clinical and Molecular Insights into Gastrointestinal Dysfunction in Myotonic Dystrophy Types 1 & 2

Authors

Janel A M Peterson
Thomas A Cooper

Publication Date

11-26-2022

Journal

International Journal of Molecular Sciences

DOI

10.3390/ijms232314779

PMID

36499107

PMCID

PMC9737721

PubMedCentral® Posted Date

11-26-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Myotonic Dystrophy, Alternative Splicing, Muscle, Skeletal, RNA-Binding Proteins, myotonic dystrophy type 1 (DM1), myotonic dystrophy type 2 (DM2), gastrointestinal dysfunction, smooth muscle, alternative splicing

Abstract

Myotonic dystrophy (DM) is a highly variable, multisystemic disorder that clinically affects one in 8000 individuals. While research has predominantly focused on the symptoms and pathological mechanisms affecting striated muscle and brain, DM patient surveys have identified a high prevalence for gastrointestinal (GI) symptoms amongst affected individuals. Clinical studies have identified chronic and progressive dysfunction of the esophagus, stomach, liver and gallbladder, small and large intestine, and rectum and anal sphincters. Despite the high incidence of GI dysmotility in DM, little is known regarding the pathological mechanisms leading to GI dysfunction. In this review, we summarize results from clinical and molecular analyses of GI dysfunction in both genetic forms of DM, DM type 1 (DM1) and DM type 2 (DM2). Based on current knowledge of DM primary pathological mechanisms in other affected tissues and GI tissue studies, we suggest that misregulation of alternative splicing in smooth muscle resulting from the dysregulation of RNA binding proteins muscleblind-like and CUGBP-elav-like is likely to contribute to GI dysfunction in DM. We propose that a combinatorial approach using clinical and molecular analysis of DM GI tissues and model organisms that recapitulate DM GI manifestations will provide important insight into defects impacting DM GI motility.