Combinatorial Effects of Ion Channel Mis-splicing As a Cause of Myopathy in Myotonic Dystrophy

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2024 Jan 2

PMID 38165037

Authors

Larissa Nitschke

Thomas A Cooper

Affiliations

Soon will be listed here.

Abstract

Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder caused by an unstable expanded CTG repeat located in the 3'-UTR of the DM1 protein kinase (DMPK) gene. The pathogenic mechanism results in misregulated alternative splicing of hundreds of genes, creating the dilemma of establishing which genes contribute to the mechanism of DM1 skeletal muscle pathology. In this issue of the JCI, Cisco and colleagues systematically tested the combinatorial effects of DM1-relevant mis-splicing patterns in vivo and identified the synergistic effects of mis-spliced calcium and chloride channels as a major contributor to DM1 skeletal muscle impairment. The authors further demonstrated the therapeutic potential for calcium channel modulation to block the synergistic effects and rescue myopathy.

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