Absence of myotonic dystrophy protein kinase (DMPK) mRNA as a result of a triplet repeat expansion in myotonic dystrophy

Abstract Myotonic dystrophy is an autosomally dominant inherited disease in which system-wide abnormalities are caused by a triplet repeal expansion within the 3′ untranslated region of the myotonic dystrophy protein kinase ( DMPK ) gene. To determine the effect an expanded repeat region has on DMPK expression, we have separated the chromosome 19 homologues from a 36-year-old woman with myotonic dystrophy into different cell lines by way of somatic cell hybridization. Hybrid DM9101 contains the normal DMPK allele (13 repeats), whereas hybrid DM1115 harbors the mutant allele (∼133 repeats). Reverse transcription/polymerase chain reaction (RT/PCR) amplification of coding sequences from the DMPK gene has shown both reduced levels of primary DMPK transcripts and impaired processing of these transcripts in hybrid cell line DM1115. These findings suggest that the presence of a large number of repeats in the 3′ untranslated region of the DMPK gene reduces both the synthesis and the processing of DMPK mRNA, resulting in undetectable levels of processed DMPK mRNA from the mutant allele.