Pathogenic DMPK RNA repeat expansion (None commonly used; often referenced as DMPK RNA repeat expansion)

Pathogenic DMPK RNA repeat expansion refers to an abnormally long sequence of CTG trinucleotide repeats in the 3' untranslated region of the DMPK gene. In healthy individuals, the DMPK gene contains 5–37 CTG repeats, but in myotonic dystrophy type 1 (DM1), this can expand to 50–1,000 or more. The transcribed RNA containing expanded CUG repeats (from the mutant allele) forms abnormal secondary structures that aggregate as nuclear RNA foci. These foci sequester critical RNA-binding proteins, especially Muscleblind-like protein 1 (MBNL1), leading to mis-splicing of multiple pre-mRNAs and causing the multisystemic features of DM1. The mechanism of disease is largely a toxic gain-of-function at the RNA level, rather than a classical receptor or enzyme target. Various therapeutic approaches are in development to target these toxic RNA species, primarily using antisense oligonucleotides or small molecules that disrupt RNA-protein interactions[2][3][4].

Other names

Expanded DMPK CTG repeat RNADMPK trinucleotide repeat expansionToxic DMPK RNAMutant DMPK mRNA with CUG repeats

Antisense oligonucleotides: bind to the mutant RNA and promote its degradation or prevent sequestration of RNA-binding proteins Small molecules: disrupt RNA-protein interactions (e.g., prevent trapping of MBNL1 by expanded CUG repeats)