Myotonic dystrophy protein kinase transcript CUG repeat expansion

The "Myotonic dystrophy protein kinase transcript CUG repeat expansion" refers to an abnormal increase in the number of CTG (cytosine-thymine-guanine) trinucleotide repeats found in the 3’ untranslated region (UTR) of the DMPK gene, which encodes the myotonic dystrophy protein kinase. In affected individuals (Myotonic dystrophy type 1 or DM1), this expansion can reach hundreds to thousands of repeats, leading to pathogenic accumulation of toxic RNA transcripts containing extended stretches of CUG repeats. These transcripts form nuclear foci that sequester key RNA-binding proteins, particularly muscleblind-like proteins (MBNL), disrupting their normal functions in mRNA splicing and processing. This toxic gain-of-function of the expanded RNA is the primary pathogenic mechanism in DM1, causing a multisystemic neuromuscular disorder characterized by myotonia, muscle wasting, cataracts, cardiac conduction defects, and other abnormalities. The expanded repeat itself is not a receptor, enzyme, or protein target but rather a pathogenic nucleic acid sequence that acts by trapping regulatory RNA-binding proteins[1][2][3][4]. No approved drugs directly target the repeat expansion, but molecular therapies aim to disrupt pathogenic RNA-protein interactions or degrade the toxic transcripts. Detection and measurement of repeat length are established molecular biomarkers for DM1 diagnosis and prognosis.

Other names

CUG repeat expansion in DMPK transcriptDMPK CUG expansionCTG repeat expansion in DMPKMyotonic dystrophy type 1 CUG expansionExpanded r(CUG)n

None (no approved drug targets the expanded CUG repeat itself directly as a classical therapeutic mechanism; research therapies aim to block RNA-protein interactions, degrade toxic RNA, or correct splicing defects)