myotonic dystrophy

Summary

Summary: An autosomal dominant neuromuscular disorder which usually presents in early adulthood, characterized by progressive muscular atrophy (most frequently involving the hands, forearms, and face), myotonia, frontal baldness, lenticular opacities, and testicular atrophy. Cardiac conduction abnormalities, diaphragmatic weakness, and mild mental retardation may also occur. Congenital myotonic dystrophy is a severe form of this disorder, characterized by neonatal MUSCLE HYPOTONIA, feeding difficulties, respiratory muscle weakness, and an increased incidence of MENTAL RETARDATION. (From Adams et al., Principles of Neurology, 6th ed, pp1423-5; Joynt, Clinical Neurology, 1997, Ch16, pp16-7)

Top Publications

  1. ncbi Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9
    C L Liquori
    Institute of Human Genetics MMC 206, 420 Delaware Street SE, University of Minnesota, Minneapolis, MN 55455, USA
    Science 293:864-7. 2001
  2. pmc Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy
    J W Miller
    Department of Molecular Genetics and Microbiology, Centers for Gene Therapy and Mammalian Genetics, University of Florida College of Medicine, Gainesville, FL 32610, USA
    EMBO J 19:4439-48. 2000
  3. pmc Muscleblind-like 2-mediated alternative splicing in the developing brain and dysregulation in myotonic dystrophy
    Konstantinos Charizanis
    Department of Molecular Genetics and Microbiology and the Center for NeuroGenetics, University of Florida, College of Medicine, Gainesville, FL 32610, USA
    Neuron 75:437-50. 2012
  4. ncbi Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy
    Charlotte Fugier
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale U964, Centre National de la Recherche Scientifique UMR7104, University of Strasbourg, Illkirch, France
    Nat Med 17:720-5. 2011
  5. pmc Aberrant alternative splicing and extracellular matrix gene expression in mouse models of myotonic dystrophy
    Hongqing Du
    RNA Center, Department of Molecular, Cell and Developmental Biology, Sinsheimer Labs, University of California, Santa Cruz, California, USA
    Nat Struct Mol Biol 17:187-93. 2010
  6. pmc Targeting nuclear RNA for in vivo correction of myotonic dystrophy
    Thurman M Wheeler
    Department of Neurology, University of Rochester, 601 Elmwood Avenue, Rochester, New York 14642, USA
    Nature 488:111-5. 2012
  7. ncbi Failure of MBNL1-dependent post-natal splicing transitions in myotonic dystrophy
    Xiaoyan Lin
    Department of Neuroscience, University of Rochester Medical Center, Rochester, NY 14642, USA
    Hum Mol Genet 15:2087-97. 2006
  8. ncbi Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy
    R S Savkur
    Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, USA
    Nat Genet 29:40-7. 2001
  9. ncbi Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene
    M Mahadevan
    Department of Microbiology and Immunology, University of Ottawa, Ontario, Canada
    Science 255:1253-5. 1992
  10. ncbi Myotonic dystrophy type 1 is associated with nuclear foci of mutant RNA, sequestration of muscleblind proteins and deregulated alternative splicing in neurons
    Hong Jiang
    Department of Neurology, University of Rochester School of Medicine and Dentistry, PO Box 673, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Hum Mol Genet 13:3079-88. 2004

Detail Information

Publications302 found, 100 shown here

  1. ncbi Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9
    C L Liquori
    Institute of Human Genetics MMC 206, 420 Delaware Street SE, University of Minnesota, Minneapolis, MN 55455, USA
    Science 293:864-7. 2001
    b>Myotonic dystrophy (DM), the most common form of muscular dystrophy in adults, can be caused by a mutation on either chromosome 19q13 (DM1) or 3q21 (DM2/PROMM)...
  2. pmc Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy
    J W Miller
    Department of Molecular Genetics and Microbiology, Centers for Gene Therapy and Mammalian Genetics, University of Florida College of Medicine, Gainesville, FL 32610, USA
    EMBO J 19:4439-48. 2000
    b>Myotonic dystrophy (DM1) is an autosomal dominant neuromuscular disorder associated with a (CTG)(n) expansion in the 3'-untranslated region of the DM1 protein kinase (DMPK) gene...
  3. pmc Muscleblind-like 2-mediated alternative splicing in the developing brain and dysregulation in myotonic dystrophy
    Konstantinos Charizanis
    Department of Molecular Genetics and Microbiology and the Center for NeuroGenetics, University of Florida, College of Medicine, Gainesville, FL 32610, USA
    Neuron 75:437-50. 2012
    The RNA-mediated disease model for myotonic dystrophy (DM) proposes that microsatellite C(C)TG expansions express toxic RNAs that disrupt splicing regulation by altering MBNL1 and CELF1 activities...
  4. ncbi Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy
    Charlotte Fugier
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale U964, Centre National de la Recherche Scientifique UMR7104, University of Strasbourg, Illkirch, France
    Nat Med 17:720-5. 2011
    b>Myotonic dystrophy is the most common muscular dystrophy in adults and the first recognized example of an RNA-mediated disease...
  5. pmc Aberrant alternative splicing and extracellular matrix gene expression in mouse models of myotonic dystrophy
    Hongqing Du
    RNA Center, Department of Molecular, Cell and Developmental Biology, Sinsheimer Labs, University of California, Santa Cruz, California, USA
    Nat Struct Mol Biol 17:187-93. 2010
    The common form of myotonic dystrophy (DM1) is associated with the expression of expanded CTG DNA repeats as RNA (CUG(exp) RNA)...
  6. pmc Targeting nuclear RNA for in vivo correction of myotonic dystrophy
    Thurman M Wheeler
    Department of Neurology, University of Rochester, 601 Elmwood Avenue, Rochester, New York 14642, USA
    Nature 488:111-5. 2012
    ..In the hereditary degenerative disease myotonic dystrophy type 1 (DM1), transcripts from the mutant allele contain an expanded CUG repeat and are retained in the ..
  7. ncbi Failure of MBNL1-dependent post-natal splicing transitions in myotonic dystrophy
    Xiaoyan Lin
    Department of Neuroscience, University of Rochester Medical Center, Rochester, NY 14642, USA
    Hum Mol Genet 15:2087-97. 2006
    In myotonic dystrophy (DM), expression of RNA containing expanded CUG or CCUG repeats leads to misregulated alternative splicing of pre-mRNA...
  8. ncbi Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy
    R S Savkur
    Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, USA
    Nat Genet 29:40-7. 2001
    b>Myotonic dystrophy type 1 (DM1) is caused by a CTG trinucleotide expansion in the 3' untranslated region of the DM protein kinase gene. People with DM1 have an unusual form of insulin resistance caused by a defect in skeletal muscle...
  9. ncbi Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene
    M Mahadevan
    Department of Microbiology and Immunology, University of Ottawa, Ontario, Canada
    Science 255:1253-5. 1992
    b>Myotonic dystrophy (DM) is the most common inherited neuromuscular disease in adults, with a global incidence of 1 in 8000 individuals...
  10. ncbi Myotonic dystrophy type 1 is associated with nuclear foci of mutant RNA, sequestration of muscleblind proteins and deregulated alternative splicing in neurons
    Hong Jiang
    Department of Neurology, University of Rochester School of Medicine and Dentistry, PO Box 673, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Hum Mol Genet 13:3079-88. 2004
    b>Myotonic dystrophy type 1 (DM1) is caused by expansion of a CTG repeat in the DMPK gene...
  11. ncbi Misregulation of miR-1 processing is associated with heart defects in myotonic dystrophy
    Frédérique Rau
    Institut de Genetique et de Biologie Moleculaire et Cellulaire IGBMC, Illkirch, France
    Nat Struct Mol Biol 18:840-5. 2011
    b>Myotonic dystrophy is an RNA gain-of-function disease caused by expanded CUG or CCUG repeats, which sequester the RNA binding protein MBNL1...
  12. ncbi Diseases of unstable repeat expansion: mechanisms and common principles
    Jennifer R Gatchel
    Department of Neuroscience, Medical Scientist Training Program, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, USA
    Nat Rev Genet 6:743-55. 2005
    ..In all these diseases, the context of the expanded repeat and the abundance, subcellular localization and interactions of the proteins and RNAs that are affected have key roles in disease-specific phenotypes...
  13. ncbi The myotonic dystrophies: molecular, clinical, and therapeutic challenges
    Bjarne Udd
    Neuromuscular Research Unit, Tampere University and University Hospital, Tampere, Finland
    Lancet Neurol 11:891-905. 2012
    b>Myotonic dystrophy is the most common type of muscular dystrophy in adults and is characterised by progressive myopathy, myotonia, and multiorgan involvement. Two genetically distinct entities have been identified...
  14. ncbi A muscleblind knockout model for myotonic dystrophy
    Rahul N Kanadia
    Department of Molecular Genetics and Microbiology, Powell Gene Therapy Center, Gainesville, FL 32610, USA
    Science 302:1978-80. 2003
    The neuromuscular disease myotonic dystrophy (DM) is caused by microsatellite repeat expansions at two different genomic loci...
  15. ncbi Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member
    J D Brook
    Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139
    Cell 68:799-808. 1992
    Using positional cloning strategies, we have identified a CTG triplet repeat that undergoes expansion in myotonic dystrophy patients. This sequence is highly variable in the normal population...
  16. ncbi Muscleblind localizes to nuclear foci of aberrant RNA in myotonic dystrophy types 1 and 2
    A Mankodi
    Department of Neurology, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Hum Mol Genet 10:2165-70. 2001
    The phenotypes in myotonic dystrophy types 1 and 2 (DM1 and DM2) are similar, suggesting a shared pathophysiologic mechanism. DM1 is caused by expansion of a CTG repeat in the DMPK gene...
  17. pmc Expansion of CUG RNA repeats causes stress and inhibition of translation in myotonic dystrophy 1 (DM1) cells
    Claudia Huichalaf
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA
    FASEB J 24:3706-19. 2010
    ..of this study was to investigate the role of the mutant CUGn RNA in the induction of stress in type 1 myotonic dystrophy (DM1) cells and in the stress-mediated inhibition of protein translation in DM1...
  18. pmc Increased steady-state levels of CUGBP1 in myotonic dystrophy 1 are due to PKC-mediated hyperphosphorylation
    N Muge Kuyumcu-Martinez
    Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA
    Mol Cell 28:68-78. 2007
    The genetic basis of myotonic dystrophy type 1 (DM1) is a CTG expansion in the 3' untranslated region (UTR) of DMPK...
  19. ncbi Myotonic dystrophy, when simple repeats reveal complex pathogenic entities: new findings and future challenges
    Géraldine Sicot
    INSERM U781, Universite Paris Descartes, Hopital Necker Enfants Malades, 156 rue de Vaugirard, Paris Cedex 15, France
    Hum Mol Genet 20:R116-23. 2011
    ..b>Myotonic dystrophy (DM), the prototypical example of an RNA-dominant disorder, is mediated by trinucleotide repeat-containing ..
  20. ncbi An unstable triplet repeat in a gene related to myotonic muscular dystrophy
    Y H Fu
    Institute for Molecular Genetics, Baylor College of Medicine, Houston, TX 77030
    Science 255:1256-8. 1992
    ..GC-rich triplet sequences were used in a scanning strategy to identify unstable genetic sequences at the myotonic dystrophy (DM) locus...
  21. pmc The RNA-binding protein Staufen1 is increased in DM1 skeletal muscle and promotes alternative pre-mRNA splicing
    Aymeric Ravel-Chapuis
    Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, K1H 8M5, Canada
    J Cell Biol 196:699-712. 2012
    In myotonic dystrophy type 1 (DM1), dystrophia myotonica protein kinase messenger ribonucleic acids (RNAs; mRNAs) with expanded CUG repeats (CUG(exp)) aggregate in the nucleus and become toxic to cells by sequestering and/or misregulating ..
  22. ncbi RNA-mediated neuromuscular disorders
    Laura P W Ranum
    Institute of Human Genetics and Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455, USA
    Annu Rev Neurosci 29:259-77. 2006
    b>Myotonic dystrophy type 1 (DM1) is caused by a CTG expansion mutation located in the 3' untranslated portion of the dystrophica myotonin protein kinase gene...
  23. pmc Rationally designed small molecules targeting the RNA that causes myotonic dystrophy type 1 are potently bioactive
    Jessica L Childs-Disney
    The Kellogg School of Science and Engineering, Department of Chemistry, The Scripps Research Institute, Scripps Florida, 130 Scripps Way 3A1, Jupiter, FL 33458, USA
    ACS Chem Biol 7:856-62. 2012
    ..study, we report that rationally designed, modularly assembled small molecules that bind the RNA that causes myotonic dystrophy type 1 (DM1) are potently bioactive in cell culture models...
  24. pmc Expanded CUG repeats Dysregulate RNA splicing by altering the stoichiometry of the muscleblind 1 complex
    Sharan Paul
    Department of Biochemistry, University of Southern California, Los Angeles, California 90033, USA
    J Biol Chem 286:38427-38. 2011
    ..the role of the splice regulator muscleblind 1 (MBNL1) in the development of RNA splice defects in myotonic dystrophy I (DM1), we purified RNA-independent MBNL1 complexes from normal human myoblasts and examined the behavior ..
  25. pmc Design of a bioactive small molecule that targets the myotonic dystrophy type 1 RNA via an RNA motif-ligand database and chemical similarity searching
    Raman Parkesh
    Department of Chemistry, Scripps Florida, 130 Scripps Way, Jupiter, Florida 33458, United States
    J Am Chem Soc 134:4731-42. 2012
    b>Myotonic dystrophy type 1 (DM1) is a triplet repeating disorder caused by expanded CTG repeats in the 3'-untranslated region of the dystrophia myotonica protein kinase (DMPK) gene...
  26. pmc Transcriptional and post-transcriptional impact of toxic RNA in myotonic dystrophy
    Robert J Osborne
    Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
    Hum Mol Genet 18:1471-81. 2009
    b>Myotonic dystrophy type 1 (DM1) is an RNA dominant disease in which mutant transcripts containing an expanded CUG repeat (CUG(exp)) cause muscle dysfunction by interfering with biogenesis of other mRNAs...
  27. ncbi Three proteins, MBNL, MBLL and MBXL, co-localize in vivo with nuclear foci of expanded-repeat transcripts in DM1 and DM2 cells
    Majid Fardaei
    Institute of Genetics, University of Nottingham, Queen s Medical Centre, Nottingham NG7 2UH, UK
    Hum Mol Genet 11:805-14. 2002
    b>Myotonic dystrophy is a complex neuromuscular disorder associated with DNA expansion mutations in two different genes...
  28. pmc The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase
    T Ishizaki
    Department of Pharmacology, Kyoto University Faculty of Medicine, Japan
    EMBO J 15:1885-93. 1996
    ..N-terminus region including a kinase domain and a part of coiled-coil structure showed strong homology to myotonic dystrophy kinase over 500 residues...
  29. pmc Pentamidine reverses the splicing defects associated with myotonic dystrophy
    M Bryan Warf
    Department of Chemistry and Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA
    Proc Natl Acad Sci U S A 106:18551-6. 2009
    b>Myotonic dystrophy (DM) is a genetic disorder caused by the expression (as RNA) of expanded CTG or CCTG repeats...
  30. ncbi Altered mRNA splicing of the skeletal muscle ryanodine receptor and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase in myotonic dystrophy type 1
    Takashi Kimura
    Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, PO Box 334, Canberra ACT 2601, Australia
    Hum Mol Genet 14:2189-200. 2005
    b>Myotonic dystrophy type 1 (DM1) is a debilitating multisystemic disorder caused by a CTG repeat expansion in the DMPK gene...
  31. ncbi Myotonic dystrophy in transgenic mice expressing an expanded CUG repeat
    A Mankodi
    Department of Neurology, School of Medicine and Dentistry, University of Rochester, Box 673, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Science 289:1769-73. 2000
    b>Myotonic dystrophy (DM), the most common form of muscular dystrophy in adult humans, results from expansion of a CTG repeat in the 3' untranslated region of the DMPK gene...
  32. pmc Analysis of exonic regions involved in nuclear localization, splicing activity, and dimerization of Muscleblind-like-1 isoforms
    Hélène Tran
    INSERM, U837, Alzheimer and Tauopathies, Lille, France
    J Biol Chem 286:16435-46. 2011
    ..Its capture by nuclear CUG expansions is one major cause for type 1 myotonic dystrophy (DM1)...
  33. ncbi Somatic instability of the expanded CTG triplet repeat in myotonic dystrophy type 1 is a heritable quantitative trait and modifier of disease severity
    Fernando Morales
    Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
    Hum Mol Genet 21:3558-67. 2012
    ..b>Myotonic dystrophy type 1 (DM1) is one such disorder that is caused by the expansion of a CTG repeat that shows extremely high ..
  34. pmc From dynamic combinatorial 'hit' to lead: in vitro and in vivo activity of compounds targeting the pathogenic RNAs that cause myotonic dystrophy
    Leslie O Ofori
    Department of Chemistry, University of Rochester, Rochester, NY 14642, USA
    Nucleic Acids Res 40:6380-90. 2012
    ..Most importantly, two compounds are able to partially restore splicing in a mouse model of DM1...
  35. ncbi Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy
    Ami Mankodi
    Department of Neurology, School of Medicine and Dentistry, University of Rochester, Box 673, 601 Elmwood Avenue, New York 14642, USA
    Mol Cell 10:35-44. 2002
    In myotonic dystrophy (dystrophia myotonica, DM), expression of RNAs that contain expanded CUG or CCUG repeats is associated with degeneration and repetitive action potentials (myotonia) in skeletal muscle...
  36. pmc Myotonic dystrophy type 1 RNA crystal structures reveal heterogeneous 1 × 1 nucleotide UU internal loop conformations
    Amit Kumar
    Department of Chemistry, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458, United States
    Biochemistry 50:9928-35. 2011
    ..conformational heterogeneity in the context of the 5'CUG/3'GUC repeat motif present in the RNA that causes myotonic dystrophy type 1 (DM1)...
  37. pmc Reversal of RNA dominance by displacement of protein sequestered on triplet repeat RNA
    Thurman M Wheeler
    Departments of Neurology, Pharmacology and Physiology, University of Rochester, Rochester, NY 14642, USA
    Science 325:336-9. 2009
    Genomic expansions of simple tandem repeats can give rise to toxic RNAs that contain expanded repeats. In myotonic dystrophy, the expression of expanded CUG repeats (CUGexp) causes abnormal regulation of alternative splicing and ..
  38. pmc Muscle weakness in myotonic dystrophy associated with misregulated splicing and altered gating of Ca(V)1.1 calcium channel
    Zhen Zhi Tang
    Department of Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA
    Hum Mol Genet 21:1312-24. 2012
    b>Myotonic dystrophy type 1 and type 2 (DM1 and DM2) are genetic diseases in which mutant transcripts containing expanded CUG or CCUG repeats cause cellular dysfunction by altering the processing or metabolism of specific mRNAs and miRNAs...
  39. ncbi Alternative splicing of PDLIM3/ALP, for α-actinin-associated LIM protein 3, is aberrant in persons with myotonic dystrophy
    Natsumi Ohsawa
    Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Komaba, Meguro ku, Japan
    Biochem Biophys Res Commun 409:64-9. 2011
    b>Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder of muscular dystrophy characterized by muscle weakness and wasting...
  40. ncbi Risk of arrhythmias in myotonic dystrophy: trial design of the RAMYD study
    Antonio Dello Russo
    Institute of Cardiology, Department of Cardiovascular Medicine, Catholic University, L go A Gemelli 8, 00168 Rome, Italy
    J Cardiovasc Med (Hagerstown) 10:51-8. 2009
    b>Myotonic dystrophy type 1 (DM1) is the most frequent muscular dystrophy in adults...
  41. pmc Pathogenic mechanisms of myotonic dystrophy
    Johanna E Lee
    Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA
    Biochem Soc Trans 37:1281-6. 2009
    DM (myotonic dystrophy) is a dominantly inherited genetic disorder that is the most common cause of muscular dystrophy in adults affecting 1 in 8500 individuals worldwide...
  42. ncbi Huntington's and myotonic dystrophy hESCs: down-regulated trinucleotide repeat instability and mismatch repair machinery expression upon differentiation
    Anna Seriola
    REGE, VUB, Brussels, Belgium
    Hum Mol Genet 20:176-85. 2011
    Huntington's disease (HD) and myotonic dystrophy (DM1) are caused by trinucleotide repeat expansions. The repeats show different instability patterns according to the disorder, cell type and developmental stage...
  43. ncbi Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing
    Nicolas Charlet-B
    Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Cell 10:45-53. 2002
    b>Myotonic dystrophy type 1 (DM1) is a dominant multisystemic disorder caused by a CTG expansion in the 3' untranslated region of the DMPK gene...
  44. pmc Muscleblind-like 1 interacts with RNA hairpins in splicing target and pathogenic RNAs
    Yuan Yuan
    Department of Molecular Genetics and Microbiology and the Genetics Institute, University of Florida, College of Medicine, Gainesville, FL, USA
    Nucleic Acids Res 35:5474-86. 2007
    ..This process is dysregulated in myotonic dystrophy because MBNL proteins are sequestered by (CUG)n and (CCUG)n RNAs expressed from mutant DMPK and ZNF9 genes, ..
  45. ncbi Colocalization of muscleblind with RNA foci is separable from mis-regulation of alternative splicing in myotonic dystrophy
    Thai H Ho
    Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    J Cell Sci 118:2923-33. 2005
    b>Myotonic dystrophy type I (DM1), which is caused by a non-coding CTG-repeat expansion in the dystrophia myotonica-protein kinase (DMPK) gene, is an RNA-mediated disease...
  46. pmc Reversal of RNA missplicing and myotonia after muscleblind overexpression in a mouse poly(CUG) model for myotonic dystrophy
    Rahul N Kanadia
    Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL 32610, USA
    Proc Natl Acad Sci U S A 103:11748-53. 2006
    ..This pathogenesis model was proposed first for the neuromuscular disease myotonic dystrophy (DM), which is associated with the expansion of structurally related (CTG)(n) and (CCTG)(n) microsatellites ..
  47. pmc Expanded CTG repeat demarcates a boundary for abnormal CpG methylation in myotonic dystrophy patient tissues
    Arturo López Castel
    Genetics and Genome Biology, Department of Pediatrics, The Hospital for Sick Children, and Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
    Hum Mol Genet 20:1-15. 2011
    b>Myotonic dystrophy (DM1) affects multiple organs, shows age-dependent progression and is caused by CTG expansions at the DM1 locus...
  48. pmc CUGBP1 overexpression in mouse skeletal muscle reproduces features of myotonic dystrophy type 1
    Amanda J Ward
    Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA
    Hum Mol Genet 19:3614-22. 2010
    The neuromuscular disease myotonic dystrophy type I (DM1) affects multiple organ systems with the major symptoms being severe muscle weakness, progressive muscle wasting and myotonia...
  49. ncbi MBNL1 is the primary determinant of focus formation and aberrant insulin receptor splicing in DM1
    Warunee Dansithong
    Department of Biochemistry and Molecular Biology, Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
    J Biol Chem 280:5773-80. 2005
    In myotonic dystrophy 1 (DM1), aggregation of the mutant DMPK RNA into RNA-protein complexes containing MBNL1 and MBNL2 has been linked to aberrant splicing of the insulin receptor (IR) RNA...
  50. ncbi Muscleblind protein, MBNL1/EXP, binds specifically to CHHG repeats
    Yoshihiro Kino
    Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Komaba, Meguro ku, Tokyo, Japan
    Hum Mol Genet 13:495-507. 2004
    b>Myotonic dystrophy (DM) type 1 is caused by an expansion of a CTG repeat in the DMPK gene and type 2 by a CCTG repeat in the ZNF9 gene...
  51. ncbi Alternative splicing of myomesin 1 gene is aberrantly regulated in myotonic dystrophy type 1
    Michinori Koebis
    Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Meguro ku, Japan
    Genes Cells 16:961-72. 2011
    b>Myotonic dystrophy type 1 (DM1) is a multisystemic disease caused by a CTG repeat expansion in the 3'-UTR of dystrophia myotonica-protein kinase. Aberrant regulation of alternative splicing is a characteristic feature of DM...
  52. ncbi Alternative splicing regulation by Muscleblind proteins: from development to disease
    Juan M Fernandez-Costa
    Department of Genetics, University of Valencia, Burjassot, Valencia, Spain
    Biol Rev Camb Philos Soc 86:947-58. 2011
    ..proteins play a critical role in hereditary diseases caused by microsatellite expansions, particularly myotonic dystrophy type 1 (DM1), in which depletion of MBNL1 activity through sequestration explains most misregulated ..
  53. pmc Muscleblind-like 1 knockout mice reveal novel splicing defects in the myotonic dystrophy brain
    Koichi Suenaga
    Division of Neurology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
    PLoS ONE 7:e33218. 2012
    b>Myotonic dystrophy type 1 (DM1) is a multi-systemic disorder caused by a CTG trinucleotide repeat expansion (CTG(exp)) in the DMPK gene...
  54. ncbi Somatic expansion behaviour of the (CTG)n repeat in myotonic dystrophy knock-in mice is differentially affected by Msh3 and Msh6 mismatch-repair proteins
    Walther J A A van den Broek
    Department of Cell Biology, UMC Nijmegen, Nijmegen Center for Molecular Life Sciences, PO Box 9101, 6500 HB Nijmegen, The Netherlands
    Hum Mol Genet 11:191-8. 2002
    The mechanism of expansion of the (CTG)n repeat in myotonic dystrophy (DM1) patients and the cause of its pathobiological effects are still largely unknown...
  55. pmc Myotonic dystrophy mouse models: towards rational therapy development
    Mário Gomes-Pereira
    INSERM U781, Universite Paris Descartes, Faculte de Medicine Necker Enfants Malades, Paris, France
    Trends Mol Med 17:506-17. 2011
    ..RNA toxicity has been best characterised in the context of myotonic dystrophy. Nearly 20 mouse models have contributed significant and complementary insights into specific aspects of ..
  56. pmc Alternative splicing dysregulation secondary to skeletal muscle regeneration
    James P Orengo
    Department of Pathology and Immunology and, Baylor College of Medicine Houston, TX 77030, USA
    Ann Neurol 69:681-90. 2011
    Dysregulation of alternative splicing has become a molecular hallmark of myotonic dystrophy type 1 (DM1), in which neonatal splice variants are expressed in adult skeletal muscle...
  57. pmc Triplet-repeat oligonucleotide-mediated reversal of RNA toxicity in myotonic dystrophy
    Susan A M Mulders
    Department of Cell Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Proc Natl Acad Sci U S A 106:13915-20. 2009
    b>Myotonic dystrophy type 1 (DM1) is caused by toxicity of an expanded, noncoding (CUG)n tract in DM protein kinase (DMPK) transcripts...
  58. ncbi Clinical and molecular aspects of the myotonic dystrophies: a review
    Laura Machuca-Tzili
    Department of Genetics, University of Nottingham, Nottingham, United Kingdom
    Muscle Nerve 32:1-18. 2005
    Type 1 myotonic dystrophy or DM1 (Steinert's disease), which is the commonest muscular dystrophy in adults, has intrigued physicians for over a century...
  59. ncbi Age and causes of death in adult-onset myotonic dystrophy
    C E de Die-Smulders
    Department of Clinical Genetics, Academic Hospital Maastricht, The Netherlands
    Brain 121:1557-63. 1998
    b>Myotonic dystrophy is a relatively common type of muscular dystrophy, associated with a variety of systemic complications. Long term follow-up is difficult because of the slow progression...
  60. ncbi Mutant human embryonic stem cells reveal neurite and synapse formation defects in type 1 myotonic dystrophy
    Antoine Marteyn
    INSERM UEVE UMR 861, I STEM AFM, 5 rue H Desbruères, Evry Cedex, France
    Cell Stem Cell 8:434-44. 2011
    b>Myotonic dystrophy type 1 (DM1) is a multisystem disorder affecting a variety of organs, including the central nervous system...
  61. ncbi Electrocardiographic abnormalities and sudden death in myotonic dystrophy type 1
    William J Groh
    Department of Medicine, Krannert Institute of Cardiology, Indiana University, Indianapolis 46202, USA
    N Engl J Med 358:2688-97. 2008
    Sudden death can occur as a consequence of cardiac-conduction abnormalities in the neuromuscular disease myotonic dystrophy type 1. The determinants of the risk of sudden death remain imprecise.
  62. pmc Structural and functional cardiac changes in myotonic dystrophy type 1: a cardiovascular magnetic resonance study
    Mieke C E Hermans
    Department of Neurology, Maastricht University Medical Centre, PO Box 5800, Maastricht, AZ, 6202, The Netherlands
    J Cardiovasc Magn Reson 14:48. 2012
    b>Myotonic dystrophy type 1 (MD1) is a neuromuscular disorder with potential involvement of the heart and increased risk of sudden death...
  63. pmc Expanded CTG repeats within the DMPK 3' UTR causes severe skeletal muscle wasting in an inducible mouse model for myotonic dystrophy
    James P Orengo
    Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 105:2646-51. 2008
    Severe skeletal muscle wasting is the most debilitating symptom experienced by individuals with myotonic dystrophy type 1 (DM1)...
  64. pmc RNase H-mediated degradation of toxic RNA in myotonic dystrophy type 1
    Johanna E Lee
    Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 109:4221-6. 2012
    b>Myotonic dystrophy type 1 (DM1) is an RNA-dominant disease caused by abnormal transcripts containing expanded CUG repeats...
  65. ncbi Cardiac manifestations of myotonic dystrophy type 1
    Helle Petri
    Department of Cardiology, National University Hospital Rigshospitalet, Copenhagen, Denmark
    Int J Cardiol 160:82-8. 2012
    ..arrhythmia, risk of sudden cardiac death (SCD) and the associations between cardiac involvement and cytosine-thymine-guanine (CTG)-repeat, neuromuscular involvement, age and gender in patients with myotonic dystrophy type 1 (MD1).
  66. ncbi Selective silencing of mutated mRNAs in DM1 by using modified hU7-snRNAs
    Virginie François
    Universite Pierre et Marie Curie PARIS6, UM76, Paris, France
    Nat Struct Mol Biol 18:85-7. 2011
    ..containing a poly-CAG antisense sequence targeting the expanded CUG repeats of mutant DMPK transcripts in myotonic dystrophy caused specific degradation of pathogenic DMPK mRNAs without affecting the products of wild-type DMPK ..
  67. pmc Triplet repeat-derived siRNAs enhance RNA-mediated toxicity in a Drosophila model for myotonic dystrophy
    Zhenming Yu
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    PLoS Genet 7:e1001340. 2011
    ..are caused by simple DNA repeat expansions; among these, non-coding CTG repeat expansions are the basis of myotonic dystrophy (DM1)...
  68. ncbi Long-term follow-up of arrhythmias in patients with myotonic dystrophy treated by pacing: a multicenter diagnostic pacemaker study
    Arnaud Lazarus
    Service de Cardiologie et de Biostatistique, Hopital Cochin, Paris, France
    J Am Coll Cardiol 40:1645-52. 2002
    We hypothesized that pacemaker (PM) implantation in patients with myotonic dystrophy (MD) with a prolonged HV interval, even asymptomatic, may protect them against sudden death related to atrioventricular (AV) block...
  69. ncbi RNA pathogenesis of the myotonic dystrophies
    John W Day
    Institute of Human Genetics, University of Minnesota, School of Medicine, Minneapolis, MN 55455, USA
    Neuromuscul Disord 15:5-16. 2005
    b>Myotonic dystrophy (dystrophia myotonica, DM) is the most common form of muscular dystrophy in adults...
  70. pmc In vivo discovery of a peptide that prevents CUG-RNA hairpin formation and reverses RNA toxicity in myotonic dystrophy models
    Amparo Garcia-Lopez
    Department of Genetics, University of Valencia, Burjassot E 46100, Spain
    Proc Natl Acad Sci U S A 108:11866-71. 2011
    b>Myotonic dystrophy type 1 (DM1) is caused by the expansion of noncoding CTG repeats in the dystrophia myotonica-protein kinase gene...
  71. ncbi Dysregulation and cellular mislocalization of specific miRNAs in myotonic dystrophy type 1
    Riccardo Perbellini
    Molecular Cardiology Laboratory, IRCCS Policlinico San Donato, 20097 Milan, Italy
    Neuromuscul Disord 21:81-8. 2011
    b>Myotonic Dystrophy Type-1 (DM1) is caused by the expansion of a CTG repeat with a peculiar pattern of multisystemic involvement affecting skeletal muscles, the heart, the eye, the central nervous system and the endocrine system...
  72. ncbi Increased temporal dispersion of myocardial repolarization in myotonic dystrophy type 1: beyond the cardiac conduction system
    Damiano Magrì
    Cardiology Department, S Andrea Hospital, Sapienza University of Rome, Rome, Italy
    Int J Cardiol 156:259-64. 2012
    The most frequently mechanism underlying sudden cardiac death in myotonic dystrophy type 1 (DM1) is bradyarrhythmias due to cardiac conduction abnormalities...
  73. pmc Identification of a (CUG)n triplet repeat RNA-binding protein and its expression in myotonic dystrophy
    L T Timchenko
    Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
    Nucleic Acids Res 24:4407-14. 1996
    b>Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease that is associated with a (CTG)n repeat expansion in the 3'-untranslated region of the myotonin protein kinase (Mt-PK) gene...
  74. pmc Genetic and chemical modifiers of a CUG toxicity model in Drosophila
    Amparo Garcia-Lopez
    Department of Genetics, University of Valencia, Burjasot, Spain
    PLoS ONE 3:e1595. 2008
    ..CUG repeat expansions interfere with the activity of human Muscleblind-like (MBNL) proteins contributing to myotonic dystrophy 1 (DM1)...
  75. pmc Correction of ClC-1 splicing eliminates chloride channelopathy and myotonia in mouse models of myotonic dystrophy
    Thurman M Wheeler
    Department of Neurology, University of Rochester, Rochester, New York 14618, USA
    J Clin Invest 117:3952-7. 2007
    In myotonic dystrophy (dystrophia myotonica [DM]), an increase in the excitability of skeletal muscle leads to repetitive action potentials, stiffness, and delayed relaxation...
  76. ncbi Myotonic dystrophy type 2: molecular, diagnostic and clinical spectrum
    J W Day
    Institute of Human Genetics, Department of Neurology, University of Minnesota School of Medicine, Minneapolis, MN 55455, USA
    Neurology 60:657-64. 2003
    b>Myotonic dystrophy types 1 (DM1) and 2 (DM2/proximal myotonic myopathy PROMM) are dominantly inherited disorders with unusual multisystemic clinical features...
  77. pmc MBNL binds similar RNA structures in the CUG repeats of myotonic dystrophy and its pre-mRNA substrate cardiac troponin T
    M Bryan Warf
    Department of Chemistry, University of Oregon, Eugene, Oregon 97403, USA
    RNA 13:2238-51. 2007
    b>Myotonic dystrophy (DM) is a genetic disorder with multisystemic symptoms that is caused by expression (as RNA) of expanded repeats of CTG or CCTG in the genome...
  78. ncbi Myotonic dystrophies and the heart
    Sunit Preet Chaudhry
    Department of Medicine, Case Western Reserve University Hospital, Cleveland, OH, USA
    Cardiol Rev 20:1-3. 2012
    b>Myotonic dystrophy (MD) is a neuromuscular disorder of autosomal dominant inheritance, which is categorized by 2 main sub-types: type 1 (MD1) and type 2 (MD2)...
  79. ncbi Frequency and stability of the myotonic dystrophy type 1 premutation
    L Martorell
    Servei de Genètica, Hospital de Sant Pau, Barcelona, Spain
    Neurology 56:328-35. 2001
    b>Myotonic dystrophy type 1 (DM1) is associated with the expansion of an unstable CTG repeat...
  80. ncbi Risk of arrhythmia in type I myotonic dystrophy: the role of clinical and genetic variables
    P Cudia
    Muscle Pathology and Neuroimmunology Unit, IRCCS Foundation, Institute of Neurology Carlo Besta, Milan 20133, Italy
    J Neurol Neurosurg Psychiatry 80:790-3. 2009
    To examine the association between the presence of arrhythmia in type 1 myotonic dystrophy (DM1) and clinical-genetic variables, evaluating their role as predictors of the risk of arrhythmia.
  81. ncbi Myotonic dystrophy: emerging mechanisms for DM1 and DM2
    Diane H Cho
    Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 1024, USA
    Biochim Biophys Acta 1772:195-204. 2007
    b>Myotonic dystrophy (DM) is a complex multisystemic disorder linked to two different genetic loci...
  82. ncbi Optimal site for atrial lead implantation in myotonic dystrophy patients: the role of Bachmann's Bundle stimulation
    Gerardo Nigro
    Chair of Cardiology, Second University of Naples Monaldi Hospital, Naples, Italy
    Pacing Clin Electrophysiol 31:1463-6. 2008
    The aim of this study was to identify the optimal site for atrial lead implantation in myotonic dystrophy type 1 (MD1) patients.
  83. pmc Intergenerational instability of the expanded CTG repeat in the DMPK gene: studies in human gametes and preimplantation embryos
    Nele De Temmerman
    Research Center for Reproduction and Genetics, University Hospital and Medical School of the Dutch speaking Brussels Free University Vrije Universiteit Brussel, Brussels, Belgium
    Am J Hum Genet 75:325-9. 2004
    ..myotonica protein kinase (DMPK) gene shows marked intergenerational and somatic instability in patients with myotonic dystrophy (DM1), when the repeat is expanded to more than approximately 55 repeats...
  84. pmc New function for the RNA helicase p68/DDX5 as a modifier of MBNL1 activity on expanded CUG repeats
    François Xavier Laurent
    Centre de Genetique Moleculaire, CNRS, UPR 3404, Avenue de Terrasse, 91198 Gif sur Yvette, Universite Paris Sud, Orsay, France
    Nucleic Acids Res 40:3159-71. 2012
    b>Myotonic Dystrophy type I (DM1) is caused by an abnormal expansion of CTG triplets in the 3' UTR of the dystrophia myotonica protein kinase (DMPK) gene, leading to the aggregation of the mutant transcript in nuclear RNA foci...
  85. ncbi The effect of atrial preference pacing on paroxysmal atrial fibrillation incidence in myotonic dystrophy type 1 patients: a prospective, randomized, single-bind cross-over study
    Vincenzo Russo
    Department of Cardiology, Second University of Naples Monaldi Hospital, Naples, Italy
    Europace 14:486-9. 2012
    ..The aim of our study was to evaluate the effect of preventive atrial pacing on AF incidence in myotonic dystrophy type I patients during a 12-month follow-up period.
  86. ncbi 107th ENMC international workshop: the management of cardiac involvement in muscular dystrophy and myotonic dystrophy. 7th-9th June 2002, Naarden, the Netherlands
    K Bushby
    Department of Neuromuscular Genetics, Institute of Human Genetics, International Centre for Life, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK
    Neuromuscul Disord 13:166-72. 2003
  87. ncbi Does Bachmann's bundle pacing prevent atrial fibrillation in myotonic dystrophy type 1 patients? A 12 months follow-up study
    Gerardo Nigro
    Cardiology, Second, University of Naples Monaldi Hospital, Naples, Italy
    Europace 12:1219-23. 2010
    Paroxysmal atrial arrhythmias occur in myotonic dystrophy type 1 (MD1) patients frequently...
  88. ncbi Myotonic dystrophy transgenic mice exhibit pathologic abnormalities in diaphragm neuromuscular junctions and phrenic nerves
    Petrica Adrian Panaite
    Neurology Service, Centre Hospitalier Universitaire Vaudois, Switzerland
    J Neuropathol Exp Neurol 67:763-72. 2008
    b>Myotonic dystrophy Type 1 (DM-1) is caused by abnormal expansion of a (CTG) repeat located in the DM protein kinase gene. Respiratory problems have long been recognized to be a major feature of this disorder...
  89. ncbi Relationships among electrophysiological findings and clinical status, heart function, and extent of DNA mutation in myotonic dystrophy
    A Lazarus
    Services de Cardiologie et de Biostatistique, Hopital Cochin, Paris, France
    Circulation 99:1041-6. 1999
    Impulse-conduction abnormalities and arrhythmias are common in myotonic dystrophy (MD)...
  90. ncbi Tissue- and age-specific DNA replication patterns at the CTG/CAG-expanded human myotonic dystrophy type 1 locus
    John D Cleary
    Program of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
    Nat Struct Mol Biol 17:1079-87. 2010
    b>Myotonic dystrophy, caused by DM1 CTG/CAG repeat expansions, shows varying instability levels between tissues and across ages within patients...
  91. ncbi Oxidative stress in myotonic dystrophy type 1
    Antonio Toscano
    Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, Messina, Italy
    Free Radic Res 39:771-6. 2005
    b>Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy affecting adults. The genetic basis of DM1 consists of a mutational expansion of a repetitive trinucleotide sequence (CTG)...
  92. ncbi Contribution of abnormal insulin secretion and insulin resistance to the pathogenesis of type 2 diabetes in myotonic dystrophy
    Gianluca Perseghin
    Section of Nutrition Metabolism and Unit of Clinical Spectroscopy, Istituto Scientifico H San Raffaele, Milan, Italy
    Diabetes Care 26:2112-8. 2003
    b>Myotonic dystrophy (MyD), the most common adult form of muscular dystrophy, is often complicated by diabetes...
  93. ncbi GSK3beta-cyclin D3-CUGBP1-eIF2 pathway in aging and in myotonic dystrophy
    Jingling Jin
    Huffington Center on Aging and Departments of Pathology and Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA
    Cell Cycle 8:2356-9. 2009
    ..un-appropriately upregulated in skeletal muscle precursors of patients affected with multisystemic disease, Myotonic Dystrophy 2 (DM2) leading to translational elevation of several proteins...
  94. pmc Heart-specific overexpression of CUGBP1 reproduces functional and molecular abnormalities of myotonic dystrophy type 1
    Misha Koshelev
    Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA
    Hum Mol Genet 19:1066-75. 2010
    b>Myotonic dystrophy type 1 (DM1) is caused by a CTG expansion within the 3'-untranslated region of the DMPK gene...
  95. pmc MSH2 ATPase domain mutation affects CTG*CAG repeat instability in transgenic mice
    Stéphanie Tomé
    INSERM, U781, Universite Paris Descartes, Hopital Necker Enfants Malades, Paris, France
    PLoS Genet 5:e1000482. 2009
    b>Myotonic dystrophy type 1 (DM1) is associated with one of the most highly unstable CTG*CAG repeat expansions...
  96. pmc The structural basis of myotonic dystrophy from the crystal structure of CUG repeats
    Blaine H M Mooers
    Department of Chemistry, Howard Hughes Medical Institute, University of Oregon, Eugene, OR 97403 1229, USA
    Proc Natl Acad Sci U S A 102:16626-31. 2005
    b>Myotonic dystrophy (DM) type 1 is associated with an expansion of (>50) CTG repeats within the 3' untranslated region (UTR) of the dystrophin myotonin protein kinase gene (dmpk)...
  97. ncbi The myotonic dystrophies: diagnosis and management
    Chris Turner
    Department of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
    J Neurol Neurosurg Psychiatry 81:358-67. 2010
    There are currently two clinically and molecularly defined forms of myotonic dystrophy: (1) myotonic dystrophy type 1 (DM1), also known as 'Steinert's disease'; and (2) myotonic dystrophy type 2 (DM2), also known as proximal myotonic ..
  98. pmc Overexpression of microRNA-206 in the skeletal muscle from myotonic dystrophy type 1 patients
    Stefano Gambardella
    Biopathology Department, Tor Vergata University, Rome, Italy
    J Transl Med 8:48. 2010
    ..that myo-miRs (myo = muscle + miR = miRNA) expression is altered in muscle from patients affected by myotonic dystrophy type 1 (DM1), the most frequently inherited neuromuscular disease in adults...
  99. ncbi Histopathological differences of myotonic dystrophy type 1 (DM1) and PROMM/DM2
    A Vihola
    Department of Neurology, Vaasa Central Hospital, Vaasa, Finland
    Neurology 60:1854-7. 2003
    ..Their results show that DM2 patients display a subpopulation of type 2 nuclear clump and other very small fibers and, hence, preferential type 2 fiber atrophy in contrast to type 1 fiber atrophy in DM1 patients...
  100. pmc Large CTG repeats trigger p16-dependent premature senescence in myotonic dystrophy type 1 muscle precursor cells
    Anne Bigot
    Universite Pierre et Marie Curie Paris 6, UMR 787, Paris, France
    Am J Pathol 174:1435-42. 2009
    A CTG repeat amplification is responsible for the dominantly inherited neuromuscular disorder, myotonic dystrophy type 1 (DM1), which is characterized by progressive muscle wasting and weakness...
  101. ncbi Pathogenic RNA repeats: an expanding role in genetic disease
    Laura P W Ranum
    Institute of Human Genetics, MMC 206, 420 Delaware St S E, University of Minnesota, Minneapolis, MN 55455, USA
    Trends Genet 20:506-12. 2004
    ..Invoking a similar loss-of-function hypothesis for the CTG expansion causing myotonic dystrophy type 1 (DM1) located in the 3' noncoding portion of a kinase gene was more difficult because DM is a ..

Research Grants70

  1. Intravenous Protein Therapy for Myotonic Dystrophy Type 1
    Richard Weisbart; Fiscal Year: 2010
    ..Our objective is to develop intravenously delivered recombinant Muscle Blind 1 (MBNL1) for patients with Myotonic Dystrophy Type 1 (DM1)...
  2. The Role of PGC-1aplha in the Pathogenesis of Myotonic Dystrophy Type 1
    Xiang Fang; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Skeletal muscle defects in myotonic dystrophy type 1 (DM1) are characterized by progressive muscle weakness and wasting, impaired mitochondrial (Mt) respiration, hyperglycemia and insulin resistance, ..
  3. The Role of Alternative Splicing Factor Sfrs10 in Neural Development
    Rahul N Kanadia; Fiscal Year: 2010
    ..There are several diseases such as Alzheimer's disease, myotonic dystrophy, spinal muscular atrophy and autism that are linked to defects in alternative splicing of specific genes or ..
  4. Alternative Splicing of the Insulin Receptor Gene
    NICHOLAS J WEBSTER; Fiscal Year: 2013
    ..More importantly, a number of disease states, such as type II diabetes, aging, myotonic dystrophy and cancer, have decreased inclusion of exon 11...
  5. Molecular mechanisms of Myotonic Dystrophy 1
    Lubov T Timchenko; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Myotonic Dystrophy type 1 (DM1) primarily affects skeletal muscle causing muscle wasting, weakness and myotonia...
  6. Antisense oligonucleotide treatment for myotonic dystrophy
    Charles A Thornton; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Myotonic dystrophy type 1 (DM1) is a relatively common form of muscular dystrophy...
  7. Function of the Six and Eya Genes in Retinal Development
    Justin P Kumar; Fiscal Year: 2012
    ..to holoprosencephaly, bilateral anophthalmia, congenital cataracts as well as non-retinal defects such as myotonic dystrophy and branchio-oto-renal syndrome...
  8. Second-site genetic modifiers of CTG/CAG microsatellite stability
    Michael Leffak; Fiscal Year: 2013
    ..In the case of myotonic dystrophy type 1 (DM1), an autosomal dominant disease of skeletal muscle with multiple phenotypes in other organs, the ..
  9. Function of the Six and Eya Genes in Retinal Development
    JUSTIN KUMAR; Fiscal Year: 2009
    ..to holoprosencephaly, bilateral anophthalmia, congenital cataracts as well as non-retinal defects such as myotonic dystrophy and branchio-oto-renal syndrome...
  10. MOLECULAR PATHOGENESIS OF MYOTONIC DYSTROPHY
    THOMAS ALEXANDER COOPER; Fiscal Year: 2013
    ABSTRACT Myotonic dystrophy (DM) is the second most common cause of muscular dystrophy and the most common cause of adult onset muscular dystrophy. The disease is dominantly inherited, multisystemic, and phenotypically variable...
  11. Recognition of Regulatory and Pathogenic RNA by Muscleblind Zinc Fingers
    PETER EDWIN WRIGHT; Fiscal Year: 2010
    ..Muscleblind plays a central role in type 1 and type 2 myotonic dystrophy, diseases that are associated with CUG and CCUG repeat expansions in untranslated messenger RNA...
  12. MOLECULAR MECHANISMS OF THE MYOTONIC DYSTROPHY MUTATION
    MANI SUBRAMANIAM MAHADEVAN; Fiscal Year: 2013
    b>Myotonic dystrophy (DM1), the most common muscular dystrophy in adults, is caused by an expanded (CTG)n tract in the 3'untranslated region (3'UTR) of the DM protein kinase (DMPK) gene resulting in nuclear entrapment of the "..
  13. Cellular Mapping of Small Molecule/Nucleic Acid Interactions
    Micah J Bodner; Fiscal Year: 2012
    ..infections also has antitumor activity and was recently identified as a lead compound for treatment of Myotonic Dystrophy, is presumed to act by binding nucleic acids but the molecular basis of its activity is not known...
  14. Development of RNA interference for treatment of myotonic dystrophy in the HSALR
    Joel R Chamberlain; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Myotonic dystrophy is the most common form of muscular dystrophy in adults, and is characterized by a wide range of clinical features including myotonia (muscle hyperexcitability), progressive ..
  15. CSHL RNA &Oligonucleotide Therapeutics Conference
    David J Stewart; Fiscal Year: 2013
    ..spinal muscular atrophy, amyotrophic lateral sclerosis, frontotemporal dementia, familial dysautonomia and myotonic dystrophy. Many of these technologies are of relevance to other diseases, and we have appended a list of other ..
  16. RNA-mediated Mechanisms in the Myotonic Dystrophies
    Charles A Thornton; Fiscal Year: 2011
    DESCRIPTION (provided by applicant): Myotonic dystrophy type 1 (DM1), the most prevalent form of muscular dystrophy in adults, leads to progressive disability and premature death...
  17. REPLICATION OF SIMPLE DNA REPEATS
    Sergei M Mirkin; Fiscal Year: 2012
    ..They include debilitating neurological disorders, such as Huntington's disease, fragile X mental retardation, myotonic dystrophy and others. This proposal is to unravel molecular mechanisms responsible for this phenomenon.
  18. Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet): Feasi
    RACHEL WIERZBA HERLIHY; Fiscal Year: 2013
    ..prevalence, demographics, healthcare coverage, and locations of care for seven other muscular dystrophies (myotonic dystrophy, congenital, Emery-Dreifuss, facioscapulo-humeral, limb-girdle, distal, and oculopharyngeal) and evaluate ..
  19. RNA DOMINANCE IN HUMAN DISEASE
    MAURICE SCOTT SWANSON; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Myotonic dystrophy (DM) is caused by the expansion of CTG and CCTG microsatellites in the non-coding regions of two different genes, DMPK and ZNF9/CNBP...
  20. Artificial site-specific RNA endonuclease as new Myotonic Dystrophy therapeutics
    Zefeng Wang; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Myotonic dystrophy (dystrophia myotonica, DM) is the most common form of muscular dystrophy in adults that affects 1 in 8500 individuals worldwide...
  21. Targeting a Toxic RNA with Small Molecules
    JOHN ANDREW BERGLUND; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Myotonic dystrophy (DM) is caused by repeat nucleotide expansions, specifically CUG and CCUG expansions in the non-coding regions of the dystrophia myotonia protein kinase gene (DMPK) and the Zn ..
  22. Allele-Selective Inhibitors for Expanded Trinucleotide Repeat Genes
    David R Corey; Fiscal Year: 2013
    ..Other disease genes contain expanded triplet repeats including ataxin-3, myotonic dystrophy protein kinase, and ataxin-7...
  23. Genome correction of Myotonic Dystrophy type 1 iPS cells by TALEN technology
    Guangbin Xia; Fiscal Year: 2013
    ..goal is to become an independent clinical research scientist and a leader in developing novel therapies for myotonic dystrophy. To continue my progress towards this goal, I propose to explore approaches to correct the mutant gene in ..
  24. Instability of Triplet Repeats in Mammalian Cells
    John H Wilson; Fiscal Year: 2013
    ..of CAG repeats in specific human genes cause numerous neurological diseases, including Huntington disease, myotonic dystrophy, and several spinocerebellar ataxias...
  25. 9th International Myotonic Dystrophy Consortium Meeting
    Richard T Moxley; Fiscal Year: 2013
    ..Summary/Abstract (Description) This application requests funding for the 9th meeting of the International Myotonic Dystrophy Consortium (IDMC-9)...
  26. Myotonic Dystrophy Type 2
    Lubov T Timchenko; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Myotonic Dystrophy type 2 (DM2) is an autosomal dominant, multisystemic disease, that primarily affects skeletal muscle causing skeletal muscle loss, muscle weakness and myotonia...
  27. 8th International Myotonic Dystrophy Consortium Meeting
    Richard T Moxley; Fiscal Year: 2011
    ..provided by applicant): This application proposes funding for the 8th meeting of the International Myotonic Dystrophy Consortium (IDMC-8)...
  28. Developing resources to alleviate muscle atrophy in FSHD by genome engineering
    Brian P Chadwick; Fiscal Year: 2013
    ..muscular dystrophy (FSHD) is the third most common inherited form of muscular dystrophy after Duchenne and Myotonic dystrophy, affecting 1 in 20,000 live births...
  29. Structural and Functional CNS Changes in Myotonic Dystrophy Types 1 and 2
    John W Day; Fiscal Year: 2011
    DESCRIPTION (provided by applicant): Myotonic Dystrophy (DM), one of the most common forms of muscular dystrophy, is a multisystemic disorder caused by mutations on either chromosome 19 (DM1) or chromosome 3 (DM2)...
  30. High Throughput Screen for Myotonic Dystrophy Type 1
    SITA contact REDDY; Fiscal Year: 2011
    DESCRIPTION (provided by applicant): Myotonic dystrophy (DM1) is the most common adult onset muscular dystrophy in humans. Currently, there is no cure or an FDA approved drug for DM1 and related diseases...
  31. Post-transcriptional regulation of gene expression in neuromuscular disease
    Eric T Wang; Fiscal Year: 2013
    Project Summary Myotonic dystrophy (DM) is the most common form of muscular dystrophy, and leads to symptoms in all muscle types, in the form of skeletal muscle wasting, cardiac arrhythmias, and gastrointestinal dysfunction...
  32. Function of Sequence-Specific Regulators of RNA Splicing
    Christopher B Burge; Fiscal Year: 2013
    ..This approach will be applied to key factors involved in development and disease, including RBFOX2 and the myotonic dystrophy (DM) related factors MBNL1 and CELF1, as well as major factors that recognize the 3'splice site and ..
  33. RNA mediated Neurotoxicity in Huntington's Disease-Like 2 and Huntington Disease
    DOBRILA DODA RUDNICKI; Fiscal Year: 2013
    ..Our preliminary data demonstrates that, like the mutation in myotonic dystrophy 1 (DM1), a disease which involves muscle more than brain, the HDL2 mutation leads to the generation of JPH3 ..
  34. Potassium channels in myotonic dystrophy type 1
    Christine Beeton; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Myotonic dystrophy type 1 (DM1) is the most common inherited neuromuscular disorder in adults. It is characterized by progressive muscle wasting and weakness in adults...
  35. Innovations in RNA Structure Prediction
    David H Mathews; Fiscal Year: 2011
    ..RNA also plays roles in human disease, including Praeder-Willi and myotonic dystrophy. Understanding and harnessing the power of RNA, e.g...
  36. MOLECULAR MECHANISMS OF MYOTONIC DYSTROPHY
    JOHN A BERGLUND; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Myotonic dystrophy (DM) is caused by nucleotide expansions of CUG and CCUG in the non-coding regions of the dystrophia myotonia protein kinase gene (DMPK) and the Zn finger 9 gene (ZNF9) respectively...
  37. Myotonic Dystrophy: Molecular Pathophysiology and CNS Effects
    Laura P W Ranum; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Myotonic dystrophy type 1 (DM1) is caused by a CTG expansion mutation located in the DMPK gene...
  38. Translational control by cis elements acting in trans
    Paul M Macdonald; Fiscal Year: 2013
    ..can influence the activity of other mRNAs, has the potential to explain RNA gain-of-function diseases such as myotonic dystrophy, spinocerebellar ataxia 8, Huntington's disease-like 2 and fragile X-associated tremor ataxia syndrome.
  39. Mechanisms of cardiovascular remodeling
    ALEXANDER RABINOVITCH; Fiscal Year: 2012
    ..Project 4 by Erin Harmon will investigate the role of a myotonic dystrophy kinase in myocyte development...
  40. Structural biology of human DNA mismatch repair machinery
    Lorena S Beese; Fiscal Year: 2010
    ..causative mutations for several meuromuscular diseases (Huntington's disease, fragile-X syndrome, and myotonic dystrophy)...
  41. Phase 2 Study of Mexiletine for the Treatment of Myotonic Dystrophy
    Richard T Moxley; Fiscal Year: 2013
    PROJECT SUMMARY Myotonic dystrophy type 1 (DM1) is an autosomal dominant, multisystem disease caused by an unstable, abnormal expansion of a trinucleotide repeat [CTG]n on chromosome 19...
  42. Mechanism of Small Molecule Mediated Rescue of Mytonic Dystrophy
    Sita Reddy; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Myotonic dystrophy (DM1) is the most common adult onset muscular dystrophy in humans. Currently, there is no cure or an FDA approved drug for DM1 and related diseases...
  43. EXPERIMENTAL THERAPEUTICS IN MOUSE MODELS OF MYOTONIC DYSTROPHY
    Thurman M Wheeler; Fiscal Year: 2012
    ..his scientific skills through studies involving transgenic mouse models and novel therapeutic agents for myotonic dystrophy type 1 (DM1)...
  44. Messenger RNA stability in myotonic dystrophy
    Carol J Wilusz; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Myotonic dystrophy (DM) is an inherited disease primarily affecting skeletal muscle...
  45. Integrative pathophysiology of myotonic dystrophy
    Charles A Thornton; Fiscal Year: 2012
    Research on myotonic dystrophy type 1 (DM1) has led to the recognition of a new mechanism for genetic disease...
  46. Role of ZNF9 in Pathogenesis of Myotonic Dystrophy Type 2 (DM2)
    Ralf Krahe; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Myotonic dystrophy (DM) is the most common adult-onset muscular dystrophy...
  47. Deep Sequencing Analysis of mRNA Isoform Expression Changes in Myotonic Dystrophy
    David Housman; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Myotonic dystrophy (DM) is the most common form of adult onset muscular dystrophy, with an incidence of about 1 in 8,000 adults...
  48. Targeting CUG Expansions for the Treatment of Myotonic Dystrophy
    Steven C Zimmerman; Fiscal Year: 2013
    ..of compounds that disrupt the poly(CUG)RNA-MBNL1 interaction in vitro and in cell culture models of myotonic dystrophy. By pursuing these aims, our goal is to rapidly validate poly(CUG)RNA as a target for the treatment of DM1, ..
  49. Paul D. Wellstone Muscular Dystrophy Cooperative Research Center
    Richard T Moxley; Fiscal Year: 2013
    ..of experience in operating our current Wellstone Center;a large group of highly motivated patients with myotonic dystrophy (DM1) eager to support translational research and participate in clinical studies;enthusiastic investigators ..
  50. Huntington's Disease Antisense Transcript
    Russell L Margolis; Fiscal Year: 2011
    ..pathogenesis have been detected at the locus of a number of repeat expansion diseases, including fragile X, myotonic dystrophy type 1, spinocerebellar ataxia type 8, and Huntington's disease-like 2...
  51. DNA repair mechanisms in trinucleotide repeat instability
    Guo Min Li; Fiscal Year: 2013
    ..of certain human neurological and neurodegenerative diseases including Huntington's disease (HD) and myotonic dystrophy. However, the mechanisms and factors that promote/prevent TNR expansions are unknown...
  52. Quantitative RNA affinity landscapes: implications for development and disease
    Nicole J Lambert; Fiscal Year: 2013
    ..For example, in myotonic dystrophy type 1 (DM1) increasing disease severity corresponds to the degree of MBNL1 depletion by toxic RNA repeats...
  53. Identification of Therapeutic Small Molecules for Myotonic Dystrophy Type 1
    Sita Reddy; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Myotonic dystrophy (DM1) is the most common adult onset muscular dystrophy in humans. Currently, there is no cure or an FDA approved drug for DM1 and related diseases...
  54. ANABOLIC ACTIONS OF INSULIN IN NEUROMUSCULAR DISEASE
    RICHARD MOXLEY; Fiscal Year: 1992
    The studies in this application focus upon the most common form of muscular dystrophy, myotonic dystrophy. This autosomal dominant disorder is felt to be due to an inherited defect in the cell membrane...
  55. The Development and Use of a Disease-Specific Instrument for Myotonic Dystophy
    CHAD RYDEL HEATWOLE; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Myotonic dystrophy is the most common adult muscular dystrophy in the world. Despite an emergent need, no disease-specific, quality-of-life instrument has ever been developed for this population...
  56. Role of FN14 in RNA Toxicity
    MANI SUBRAMANIAM MAHADEVAN; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Myotonic dystrophy (DM1), the most common form of muscular dystrophy in adults and children, is a multi- systemic, autosomal dominant genetic disorder caused by a mutation that leads to the production ..
  57. SK CHANNELS IN HYPEREXCITABLE SKELETAL MUSCLE
    John Adelman; Fiscal Year: 2001
    ..4). DMAHP (myotonic dystrophy associated homeodomain protein or DMPK (myotonic dystrophy protein kinase) regulates SK channel expression...
  58. Biochemical analyses of muscleblind complexes in myotonic dystrophy
    Sita Reddy; Fiscal Year: 2012
    ..of altered RNA splicing that are controlled by the formation of pathological MBNL1 mega-complexes in myotonic dystrophy 1 (DM1) patient cells...
  59. MECHANISM OF MIS-SPLICING IN MYOTONIC DYSTROPHY 1
    MUGE KUYUMCU MARTINEZ; Fiscal Year: 2007
    b>Myotonic dystrophy (DM) is an autosomal dominant disorder affecting 1 in 8500 people worldwide. Individuals with DM exhibit progressive muscular dystrophy, arrhythmias and CNS damage...
  60. INTERACTIONS OF MYOTONIC DYSTROPHY PROTEIN KINASE
    Henry Epstein; Fiscal Year: 2004
    DESCRIPTION (adapted from applicant's abstract): Myotonic Dystrophy Protein Kinase (DMPK) is encoded by the Myotonic Dystrophy 1 (DM1) locus...
  61. DNA CONFORMATION, TRIPLET EXPANSION, AND HUMAN DISEASE
    Robert Wells; Fiscal Year: 1999
    ..mutations responsible for seven human genetic diseases; including Fragile X-syndrome (FRAXA and FRAXE), myotonic dystrophy, Kennedy's disease, huntington's disease, spinocerebellar ataxia type 1 (SCA1), and dentatorubral ..
  62. High Performance Digital NMR Spectrometer Console
    PETER EDWIN WRIGHT; Fiscal Year: 2010
    ..The enhanced capabilities of the instrument will facilitate ongoing and future research on the underlying molecular basis of cancer, myotonic dystrophy, neurodegeneration, amyloid diseases, and infectious disease.
  63. Modulating the levels of a splicing factor to reveal the complexities of a splici
    STACEY DENISE WAGNER; Fiscal Year: 2013
    ..is an alternative splicing factor whose improper sequestration is a primary component of the genetic disease myotonic dystrophy (DM)...
  64. Fragility and Instability at Hairpin-Forming Trinucleotide Repeats in Yeast
    Catherine H Freudenreich; Fiscal Year: 2010
    ..expand in the human genome to cause 17 inherited human diseases, including Huntington's disease, myotonic dystrophy, and spinocerebellar ataxias...
  65. PLAN FOR A TRIAL OF DHEAS IN MYOTONIC DYSTROPHY
    Charles Thornton; Fiscal Year: 2000
    ..no effective treatment that improves or even slows the progressive muscle wasting and weakness that occur in myotonic dystrophy (dystrophica myotonia, DM), the most common inherited muscle disease in adults...
  66. Mechanisms of decay of toxic CUGn RNA in DM1 patients
    Lubov Timchenko; Fiscal Year: 2009
    DESCRIPTION (provided by applicant): Myotonic Dystrophy 1 (DM1) is a complex, inherited, neuro-muscular disease without cure...
  67. Triplet Repeat Instability in Human Tissue Culture Cells
    Brian Farrell; Fiscal Year: 2007
    ..cause at least 15 neurodegenerative disorders, including Huntington's disease (HD), Friedreich ataxia, myotonic dystrophy and >90% of inherited spinocerebellar ataxias (SCAs)...
  68. Pathogenesis of Myopathy in Models of Myotonic Dystrophy
    Charles Thornton; Fiscal Year: 2009
    DESCRIPTION (provided by applicant): Myotonic dystrophy type 1 [DM1] leads to maldevelopment, myotonia, and wasting of skeletal muscle. DM1 is caused by an unstable CTG repeat expansion in the 3'untranslated region of DMPK...
  69. The Role of RNA-Binding Proteins in Myogenesis
    Lubov Timchenko; Fiscal Year: 2007
    ..and is implicated in the delay of skeletal muscle differentiation in patients with a neuro-muscular disease, Myotonic Dystrophy. Analysis of CUGBP1 expression during differentiation course revealed a dramatic induction of CUGBP1 mRNA ..
  70. Molecular pathophysiology of facioscapulohumeral muscul*
    Yi Wen Chen; Fiscal Year: 2003
    ..FSHD) is one of the most common inherited muscle diseases following Duchenne muscular dystrophy and myotonic dystrophy. The disorder is autosomal dominant with nearly complete penetrance (95%) by age 20...