Myotonic dystrophy protein kinase (DMPK) gene CTG expansion locus (DMPK CTG expansion)

The Myotonic dystrophy protein kinase (DMPK) gene CTG expansion locus is a genomic region in the 3' untranslated region of the DMPK gene on chromosome 19 (NIH, 2023). In healthy individuals, this locus contains 5 to 34 CTG repeats, but in Myotonic Dystrophy Type 1 (DM1), it expands to 50 or more repeats, sometimes reaching several thousand (StatPearls, 2023). These expanded repeats are transcribed into toxic mRNA containing CUG expansions that form stable hairpin structures (PubMed, 2012). These structures sequester RNA-binding proteins, primarily Muscleblind-like 1 (MBNL1), leading to widespread alternative splicing defects (UniProt, 2024). This spliceopathy causes the multi-systemic symptoms of DM1, including myotonia, muscle wasting, and cardiac conduction defects. Therapeutic strategies target this locus using antisense oligonucleotides (ASOs) or siRNAs to degrade the toxic mRNA (Avidity Biosciences, 2023). Other approaches involve small molecules that disrupt the toxic RNA-protein interactions or modulate downstream signaling pathways like GSK3-beta (Dyne Therapeutics, 2024).

Other names

DM1 locusDMPK 3' UTR CTG repeatMyotonic dystrophy type 1 locusCUG expansion locus

Antisense-mediated RNA degradation, siRNA-mediated RNA interference, and small molecule inhibition of downstream kinases or disruption of RNA-protein sequestration.