Background: Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disorder with defects in many tissues, including skeletal muscle myotonia, progressive myopathy, and abnormalities in heart, brain, and endocrine systems. It is associated with a trinucleotide repeat occurring in the 3' (UTR) untranslated region of the myotonic dystrophy protein kinase (DMPK) gene. Several studies have been carried out to determine DMPK gene expression in muscle and non-muscle tissues.
Methods: DMPK gene expression was determined in lymphocytes of adult-onset patients with DM and normal controls. To quantitate total locus expression as well as allele-specific mRNA levels, semiquantitative RT-PCR assay was used. Allele-specific expression was analyzed using a Bpm1 polymorphism located at exon 10 of the DMPK gene.
Results: In heterozygous patients with DM, we observed a fourfold difference between mRNA levels produced by the Bpm1-undigested allele (187 bp) compared to the Bpm1-digested allele (136 bp). By using (CTG) trinucleotide (with cytosine, thymine, and guanine) expansion polymorphism, it was shown that the down-regulated allele corresponds to the mutant allele. Interestingly, the reduction in the mutant allele-transcript levels is compensated by an increase of the wild-type allele, yielding no significant differences in total locus mRNA amount between patients and normal individuals.
Conclusions: These results suggest that the expression of the two alleles at the DMPK locus in lymphocytes is coordinated. The reduction in mutant-allele transcript levels is compensated by an increase in wild-type allele mRNA levels.