title: Myotonic dystrophy: absence of CTG enlarged transcript in congenital forms, and low expression of the normal allele.
abstract: Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease. The mutation has been identified as an unstable trinucleotide CTG repeat in a sequence encoding a putative cAMP-dependent protein kinase. The CTG repeat varies in length between affected siblings, and generally increases through generations in parallel with increasing severity of the disease. Congenital myotonic dystrophy, which represents the most severe phenotype, is exclusively maternally inherited. In this report, we show, by Northern blot analysis, that no mutated enlarged transcript is detectable in a 20-week-old DM fetus and in two congenitally affected infants. Furthermore, in skeletal and cardiac muscle of the DM fetus, we observed by RNA analysis, including Northern blot and RT-PCR, an unexpectedly low expression of the paternal wild type allele. Varying degrees of expression of the mutant and/or the normal allele might therefore account for the characteristic features of the congenital form and the extreme variability of the disease.
authors.affiliation: INSERM U73, Château de Longchamp, Bois de Boulogne, Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: Hofmann-Radvanyi
authors.forename: C
authors.initials: C
authors.lastname: Lavedan
authors.forename: J P
authors.initials: JP
authors.lastname: Rabès
authors.forename: D
authors.initials: D
authors.lastname: Savoy
authors.forename: C
authors.initials: C
authors.lastname: Duros
authors.forename: K
authors.initials: K
authors.lastname: Johnson
authors.forename: C
authors.initials: C
authors.lastname: Junien
mesh_terms: D000483:Alleles; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics*; D004247:DNA / Q000032:analysis; D017931:DNA Primers; D015870:Gene Expression; D005799:Genes, Dominant; D006801:Humans; D007231:Infant, Newborn; D008969:Molecular Sequence Data; D009132:Muscles / Q000201:enzymology; D009154:Mutation; D009206:Myocardium / Q000201:enzymology; D009223:Myotonic Dystrophy / Q000151:congenital / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000032:analysis; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D012313:RNA; D004247:DNA; D017868:Cyclic AMP-Dependent Protein Kinases