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Insulin Receptor Splicing Alteration in Myotonic Dystrophy Type 2
| Content Provider | CiteSeerX |
|---|---|
| Author | Day, J. W. |
| Abstract | Myotonic dystrophy (DM) is caused by either an untranslated CTG expansion in the 3 ′ untranslated region of the DMPK gene on chromosome 19 (dystrophia myotonica type 1 [DM1]), or an untranslated CCTG tetranucleotide repeat expansion in intron 1 of the ZNF9 gene on chromosome 3 (dystrophia myotonica type 2 [DM2]). RNA-binding proteins adhere to transcripts of the repeat expansions that accumulate in the nucleus, and a trans-dominant dysregulation of pre-mRNA alternative splicing has been demonstrated for several genes. In muscle from patients with DM1, altered insulin-receptor splicing to the nonmuscle isoform corresponds to the insulin insensitivity and diabetes that are part of the DM phenotype; because of insulin-receptor species differences, this effect is not seen in mouse models of the disease. We now demonstrate that comparable splicing abnormalities occur in DM2 muscle prior to the development of muscle histopathology, thus demonstrating an early pathogenic effect of RNA expansions. Myotonic dystrophy type 1 (DM1 [MIM 160900]) and myotonic dystrophy type 2 (DM2 [MIM 602668]) are complex multisystemic disorders with a constellation of unusual and seemingly unrelated clinical features, in-cluding myotonia (inability of muscle to relax), muscular dystrophy with characteristic histological features, dis- |
| File Format | |
| Access Restriction | Open |
| Subject Keyword | Myotonic Dystrophy Type Insulin Receptor Splicing Alteration Dystrophia Myotonica Type Myotonic Dystrophy Trans-dominant Dysregulation Insulin Insensitivity Muscle Histopathology Untranslated Cctg Tetranucleotide Repeat Expansion Dm Phenotype Nonmuscle Isoform Insulin-receptor Splicing Muscular Dystrophy Rna Expansion Insulin-receptor Specie Difference Untranslated Ctg Expansion Dm1 Mim Characteristic Histological Feature Unrelated Clinical Feature Dm2 Mim Several Gene Pre-mrna Alternative Splicing In-cluding Myotonia Rna-binding Protein Dmpk Gene Complex Multisystemic Disorder Early Pathogenic Effect Untranslated Region Znf9 Gene Dm2 Muscle Mouse Model Repeat Expansion |
| Content Type | Text |
