P. Steinbach et al., THE DMPK GENE OF SEVERELY AFFECTED MYOTONIC-DYSTROPHY PATIENTS IS HYPERMETHYLATED PROXIMAL TO THE LARGELY EXPANDED CTG REPEAT, American journal of human genetics, 62(2), 1998, pp. 278-285
Using methylation-sensitive restriction enzymes, we characterized the
methylation pattern on the 5' side of the CTG repeat in the DMPK gene
of normal individuals and of patients affected with myotonic dystrophy
showing expansions of the repetitive sequence. The gene segment analy
zed corresponds to the genomic SacI-HindIII fragment carrying exons 11
-15. These is constitutive methylation in intron 12 at restriction sit
es of SacII and HhaI, localized 1,159-1,232 bp upstream of the CTG rep
eat, whereas most, if not all, of the other sites of SacII, HhaI, and
HpaII in this region are unmethylated, in normal individuals and most
of the patients. In a number of young and severely affected patients,
however, complete methylation of these restriction sites was found in
the mutated allele, In most of these patients, the onset of the diseas
e was congenital. Preliminary in vivo footprinting data gave evidence
for protein-DNA contact in normal genes at an Spl consensus binding si
te upstream of the CTG repeat and for a significant reduction of this
interaction in cells with a hypermethylated DMPK gene.