Myotonic dystrophy is associated with a reduced level of RNA from the DMWDallele adjacent to the expanded repeat

Myotonic dystrophy is caused by the expansion of a CTG repeat sequence, The mechanism by which this expanded repeat produces the pathophysiology of my otonic dystrophy is not clear, It has been shown previously that expansion of the repeat produces allele-specific effects on transcripts from two gene s, DMPK and SIX5. We have examined the effect of repeat expansion on the le vel of RNA from a third gene, DMWD. We have identified a polymorphism in th is gene and developed a quantitative allele-specific assay for DMWD RNA lev els, which we have applied to nuclear and cytoplasmic fractions of RNA from DM cell lines, We have found that the level of the DM-associated allele in the cytoplasm of DM cell lines is reduced by 20-50% compared with the wild -type allele, similar to the level of reduction found for SIX5 in allele-sp ecific analysis, However, no such reduction is observed in RNA from the nuc lear fraction of DM cell lines. This may reflect the complex nature of proc essing transcriptional units at the DM locus.