title: Myotonic dystrophies: An update on clinical aspects, genetic, pathology, and molecular pathomechanisms.
abstract: Myotonic dystrophy (DM) is the most common adult muscular dystrophy, characterized by autosomal dominant progressive myopathy, myotonia and multiorgan involvement. To date two distinct forms caused by similar mutations have been identified. Myotonic dystrophy type 1 (DM1, Steinert's disease) is caused by a (CTG)n expansion in DMPK, while myotonic dystrophy type 2 (DM2) is caused by a (CCTG)n expansion in ZNF9/CNBP. When transcribed into CUG/CCUG-containing RNA, mutant transcripts aggregate as nuclear foci that sequester RNA-binding proteins, resulting in spliceopathy of downstream effector genes. However, it is now clear that additional pathogenic mechanism like changes in gene expression, protein translation and micro-RNA metabolism may also contribute to disease pathology. Despite clinical and genetic similarities, DM1 and DM2 are distinct disorders requiring different diagnostic and management strategies. This review is an update on the recent advances in the understanding of the molecular mechanisms behind myotonic dystrophies. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.
authors.affiliation: Department of Neurology, IRCCS Policlinico San Donato, University of Milan, San Donato Milanese, Milan, Italy; Laboratory of Muscle Histopathology and Molecular Biology, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy. Electronic address: giovanni.meola@unimi.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Meola
authors.affiliation: Laboratory of Muscle Histopathology and Molecular Biology, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy. Electronic address: rosanna.cardani@guest.unimi.it.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Cardani
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D009223:Myotonic Dystrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D065636:Myotonin-Protein Kinase / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019680:Trinucleotide Repeat Expansion
chemical_list: C433227:CNBP protein, human; C585517:DMPK protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D065636:Myotonin-Protein Kinase
keywords: Clinical finding; Molecular mechanism; Muscle biopsy; Myotonic dystrophy type 1; Myotonic dystrophy type 2; Pathology