Myotonic dystrophy protein kinase (DMPK) gene expression in lymphocytes ofpatients with myotonic dystrophy

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 syst ems. 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 u sed. Allele-specific expression was analyzed using a Bpm1 polymorphism loca ted at exon 10 of the DMPK gene. Results, In heterozygous patients with DM, we observed a fourfold differenc e between mRNA levels produced by the Bpm1-undigested allele (187 bp) compa red to the Bpm1-digested allele (136 bp). By using (CTG) trinucleotide (wit h 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 to tal locus mRNA amount between patients and normal individuals, Conclusions. These results suggest that the expression of the two alleles a t the DMPK locus in lymphocytes is coordinated. The reduction in mutant-all ele transcript levels is compensated by an increase in wild-type allele mRN A levels, (C) 2001 IMSS. Published by Elsevier Science Inc.