MYOTONIC-DYSTROPHY - ABSENCE OF CTG ENLARGED TRANSCRIPT IN CONGENITALFORMS, AND LOW EXPRESSION OF THE NORMAL ALLELE

Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease . The mutation has been identified as an unstable trinucleotide CTG re peat in a sequence encoding a putative cAMP-dependent protein kinase. The CTG repeat varies in length between affected siblings, and general ly increases through generations in parallel with increasing severity of the disease. Congenital myotonic dystrophy, which represents the mo st severe phenotype, is exclusively maternally inherited. In this repo rt, we show, by Northern blot analysis, that no mutated enlarged trans cript is detectable in a 20-week-old DM fetus and in two congenitally affected infants. Furthermore, in skeletal and cardiac muscle of the D M fetus, we observe by RNA analysis, including Norhern blot and RT-PCR , an unexpectedly low expression of the paternal wild type allele. Var ying degrees of expression of the mutant and/or the normal allele migh t therefore account for the characteristic features of the congenital form and the extreme variability of the disease.