PURPOSE OF REVIEW: The aim of this review is to highlight recent progress in elucidating the disease mechanism in myotonic dystrophy type 1 and type 2. RECENT FINDINGS: Research on myotonic dystrophy has led to the recognition of a novel RNA-mediated disease process. In myotonic dystrophy it is the RNA rather than protein product of a disease gene that has deleterious effects on muscle cells. These unusual RNAs, which contain a long expanse of CUG or CCUG repeats, have far reaching effects on cell function by influencing the biogenesis of other cellular RNAs. One aspect of RNA metabolism that is particularly affected is the regulation of alternative splicing. By this mechanism, effects of myotonic dystrophy repeat expansions impact many different pathways, triggering a complex set of signs and symptoms. SUMMARY: The genetic lesion in myotonic dystrophy does not eliminate an essential muscle protein. Instead, it induces a defect of RNA processing that is potentially reversible. The nature of this disease process raises the possibility that myotonic dystrophy, among genetic disorders, may be unusually susceptible to treatment using non-gene-therapy approaches.
PURPOSE OF REVIEW: The aim of this review is to highlight recent progress in elucidating the disease mechanism in myotonic dystrophy type 1 and type 2. RECENT FINDINGS: Research on myotonic dystrophy has led to the recognition of a novel RNA-mediated disease process. In myotonic dystrophy it is the RNA rather than protein product of a disease gene that has deleterious effects on muscle cells. These unusual RNAs, which contain a long expanse of CUG or CCUG repeats, have far reaching effects on cell function by influencing the biogenesis of other cellular RNAs. One aspect of RNA metabolism that is particularly affected is the regulation of alternative splicing. By this mechanism, effects of myotonic dystrophy repeat expansions impact many different pathways, triggering a complex set of signs and symptoms. SUMMARY: The genetic lesion in myotonic dystrophy does not eliminate an essential muscle protein. Instead, it induces a defect of RNA processing that is potentially reversible. The nature of this disease process raises the possibility that myotonic dystrophy, among genetic disorders, may be unusually susceptible to treatment using non-gene-therapy approaches.
Authors: Shahinaz M Gadalla; Marie Lund; Ruth M Pfeiffer; Sanne Gørtz; Christine M Mueller; Richard T Moxley; Sigurdur Y Kristinsson; Magnus Björkholm; Fatma M Shebl; James E Hilbert; Ola Landgren; Jan Wohlfahrt; Mads Melbye; Mark H Greene Journal: JAMA Date: 2011-12-14 Impact factor: 56.272
Authors: Zhen Zhi Tang; Viktor Yarotskyy; Lan Wei; Krzysztof Sobczak; Masayuki Nakamori; Katy Eichinger; Richard T Moxley; Robert T Dirksen; Charles A Thornton Journal: Hum Mol Genet Date: 2011-12-02 Impact factor: 6.150
Authors: Peter C Gareiss; Krzysztof Sobczak; Brian R McNaughton; Prakash B Palde; Charles A Thornton; Benjamin L Miller Journal: J Am Chem Soc Date: 2008-12-03 Impact factor: 15.419
Authors: Tri Indah Winarni; Weerasak Chonchaiya; Tanjung Ayu Sumekar; Paul Ashwood; Guadalupe Mendoza Morales; Flora Tassone; Danh V Nguyen; Sultana M H Faradz; Judy Van de Water; Kylee Cook; Alyssa Hamlin; Yi Mu; Paul J Hagerman; Randi J Hagerman Journal: Am J Med Genet A Date: 2012-08-17 Impact factor: 2.802