Characterization of the myotonic dystrophy region predicts multiple protein isoform-encoding mRNAs

The mutation underlying myotonic dystrophy (DM) has been identified as an expansion of a polymorphic CTG–repeat in a gene encoding protein kinase activity. Brain and heart transcripts of the DM–kinase ( DMR–B15 ) gene are subject to alternative RNA splicing in both human and mouse. The unstable [CTG] 5–30 motif is found uniquely in humans, although the flanking nucleotides are also present in mouse. Characterization of the DM region of both species reveals another active gene ( DMR–N9 ) in close proximity to the kinase gene. DMR–N9 transcripts, mainly expressed in brain and testis, possess a single, large open reading frame, but the function of its protein product is unknown. Clinical manifestation of DM may be caused by the expanded CTG–repeat compromising the (alternative) expression of DM–kinase or DMR–N9 proteins.