title: [From gene to disease; altered RNA processing as a cause of myotonic dystrophy type 1].
abstract: Myotonic dystrophy type 1 is the most common muscular dystrophy in adults. Clinical features are variable and include myotonia, a slowly progressive muscle weakness and organ complications. Inheritance is autosomal dominant and characterised by anticipation, i.e. an earlier age of onset and more severe clinical course in subsequent generations, and exclusively maternal transmission of the most severe congenital type. The myotonic dystrophy type 1 mutation is an untranslated cytosine-thymine-guanine (CTG) expansion in the 'dystrophia myotonica-protein kinase' (DMPK) gene. The repeat expansion alters RNA processing, including alternative splicing of several genes and the expression of several transcription factors. Furthermore, reduced DMPK protein levels are present and it is proposed that the expanded CTG repeat has a local effect on genes in the myotonic dystrophy type 1 region by altering the chromatin structure.
authors.affiliation: Academisch Ziekenhuis Maastricht, Postbus 5800, 6202 AZ Maastricht. christine.dedie@gen.unimaas.nl
authors.forename: C E M
authors.initials: CE
authors.lastname: de Die-Smulders
authors.forename: C G
authors.initials: CG
authors.lastname: Faber
authors.forename: H J M
authors.initials: HJ
authors.lastname: Smeets
mesh_terms: D017668:Age of Onset; D002843:Chromatin / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D009154:Mutation; D009223:Myotonic Dystrophy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
chemical_list: D002843:Chromatin; D016601:RNA-Binding Proteins; D017346:Protein Serine-Threonine Kinases