Alternative Splicing of SORBS1 Affects Neuromuscular Junction Integrity in Myotonic Dystrophy Type 1.

ABSTRACT:

Background

Myotonic dystrophy type 1 (DM1) is a multisystemic neuromuscular disorder characterized by CTG repeat expansion in the 3' untranslated region of the dystrophia myotonica protein kinase coding gene. The presence of expanded CTG repeats in DMPK mRNAs leads to the sequestration of RNA-binding factors such as the Muscleblind-like (MBNL) proteins, resulting in widespread splicing defects that contribute to progressive muscle weakness and myotonia. Previously, we identified misregulation of SORBS1 exon 25 splicing in both DM1 and MBNL1/2 double-knockout human-induced pluripotent stem cells (hiPSC)-derived skeletal muscle cells, suggesting a potential role in DM1 physiopathology.

Methods

We investigated SORBS1 exon 25 splicing misregulation in human skeletal muscle biops

SUBMITTER: Hermitte C 

PROVIDER: S-EPMC12624223 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature