A study of DNA methylation in myotonic dystrophy.

Abstract

We have examined the hypothesis that the severe congenital form of myotonic dystrophy is caused by genomic imprinting at the level of differential DNA methylation of maternal and paternal alleles. Probes encompassing the 5', central, and 3' regions of the myotonic dystrophy protein kinase gene were used on blots of blood DNA from congenital and adult onset patients, digested with combinations of methylation sensitive and insensitive restriction enzymes. We observed similar patterns of methylation in each of the different classes of patient, and found no methylation differences between paternally and maternally derived alleles. Within the limitations of the experiment, our results provide no evidence for a role for genomic imprinting in congenital myotonic dystrophy and suggest that the explanation for this form of the disease will be found elsewhere. (J Med Genet 1993;30:189-92)

Epigenetic modifications in trinucleotide repeat diseases

“…Both DM1 fetus and adult samples were not methylated downstream of the TNR [85]. Earlier reports show conflicting data, but these studies used small sample cohorts and different tissues [86][87][88]. It is clear, however, that differential DNA methylation in regions flanking the TNR in DMPK, particularly in different tissues, is likely to be an important contributing factor to the variable clinical outcome of this disease.…”

Triplet repeat disorders: discussion of molecular mechanisms

“…It was shown that CTG repeats affect chromatin structure [31], but it seems that the repeat does not affect DMPK transcription, because mutant transcripts were detected by reverse transcription-polymerase chain reaction and Northern analysis [30]. Some studies demonstrated that a DNA region containing long CTG repeats could be hypermethylated [32], affecting transcription in the region of CTG repeats, but others found no effect of CTG repeats on DNA methylation [33]. Several reports described abnormalities in DMPK RNA processing.…”

Is myotonic dystrophy a single-gene disorder?

“…The (CTG),, repeat might also cause changes in methylation status within the region. One study failed to detect such changes between normal and DM material, but the analysis was not comprehensive [23]. Congenitally affected muscle, kidney and pancreas show delay in maturation [24,25], and it is possible that expression of DMAHP plays a particular role in early development of these tissues (DMAHP has already been shown to be expressed in them [17]).…”