EFFECT OF THE MYOTONIC-DYSTROPHY (DM) MUTATION ON MESSENGER-RNA LEVELS OF THE DM GENE

Myotonic dystrophy (DM) results from the amplification of an unstable CTG repeat in the 3' untranslated region of a transcript encoding a pu tative serine/threonine kinase. We have analysed the amplification of the repeat and the steady state levels of the DM kinase (DMK) mRNA in tissues and cell lines from normal and congenital DM individuals. Sout hern blot analysis of DNA samples from a severely affected neonate sho ws somatic heterogeneity of the repeat in all tissues studied. RNA ana lyses on these tissues show a marked increase in DMK steady state mRNA levels. We demonstrate that the mutant DMK allele is expressed regard less of the number of CTG repeats and that the increase in DMK mRNA le vels is due to elevated mutant mRNA levels. We postulate that elevated DMK levels explains the dominant inheritance pattern of DM.