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Trinucleotide Repeat ExpansionTrinucleotide RepeatsGenes, DominantFriedreich AtaxiaMyotonic DystrophyDNA Repeat ExpansionPedigreeSpinocerebellar DegenerationsFragile X SyndromeHuntington DiseaseFragile X Mental Retardation ProteinIron-Binding ProteinsAllelesMutationCrosses, GeneticGenetic LinkageRepetitive Sequences, Nucleic AcidSpinocerebellar AtaxiasBase SequenceMachado-Joseph DiseasePhenotypePolycystic Kidney, Autosomal DominantChromosome MappingMolecular Sequence DataGenetic MarkersHeredodegenerative Disorders, Nervous SystemPlant DiseasesNerve Tissue ProteinsMicrosatellite RepeatsAnticipation, GeneticGenomic InstabilityDNACerebellar AtaxiaFrontotemporal DementiaAge of OnsetFlap EndonucleasesIntranuclear Inclusion BodiesGenes, PlantGenotypeNucleic Acid ConformationTandem Repeat SequencesInverted Repeat SequencesMinisatellite RepeatsRNA-Binding ProteinsPolymerase Chain ReactionGenetic Diseases, InbornMuscular Dystrophy, OculopharyngealChromosome FragilityPolymorphism, GeneticImmunity, InnateDNA Mutational AnalysisAmyotrophic Lateral SclerosisNuclear ProteinsMice, Inbred StrainsNeurodegenerative DiseasesProteinsProtein-Serine-Threonine KinasesHeterozygoteSequence Analysis, DNAHybridization, GeneticMice, TransgenicExonsPeptidesHaplotypesModels, GeneticChromosomes, PlantDNA RepairDNA PrimersAmino Acid SequenceMyotonic DisordersReceptors, AndrogenDisease Models, AnimalRNA, MessengerBreedingTranscription, GeneticTRPP Cation ChannelsLod ScoreGenome, HumanPlant LeavesMyoclonic Epilepsies, ProgressiveDNA-Binding ProteinsCell LineMutS Homolog 2 ProteinGenetic TestingDNA ReplicationRetinitis PigmentosaGene FrequencySpecies SpecificitySaccharomyces cerevisiaeGenetic VariationRepetitive Sequences, Amino AcidNucleic Acid HeteroduplexesRNAAtaxiaSequence DeletionDNA, Satellite
MyotonicInheritanceProteinAlleleChromosomeProteinsDisordersRegionCopiesMuscleHumanExpressionGeneralStructureDystrophia myotonDisorderMutationToxicCorrelateInhibitorAbnormalEnzymeDiseaseMiceGeneticTypeLeadsModelForm
Myotonic5
  • Myotonin-protein kinase (MT-PK) also known as myotonic dystrophy protein kinase (MDPK) or dystrophia myotonica protein kinase (DMPK) is an enzyme that in humans is encoded by the DMPK gene. (wikipedia.org)
  • However, an in vivo demonstration of the phosphorylation of these substrates by DMPK remains to be established, and a link between these substrates and the clinical manifestations of myotonic dystrophy (DM) is unclear. (wikipedia.org)
  • Expansion of this unstable motif to 50-5,000 copies causes myotonic dystrophy type I, which increases in severity with increasing repeat element copy number. (wikipedia.org)
  • Myotonic dystrophy (DM) 1 is an autosomal dominant neuromuscular disorder affecting approximately 1 in 8000 individuals. (wikipedia.org)
  • Myotonic dystrophy is rare, autosomal dominant muscle disorder. (msdmanuals.com)
Inheritance1
  • Hereditary disorders are passed down from parent to offspring via different patterns of inheritance, including autosomal dominant , autosomal recessive , X-linked , and mitochondrial inheritance . (amboss.com)
Protein6
  • The dmpk gene product is a Ser/Thr protein kinase homologous to the MRCK p21-activated kinases and Rho kinase family. (wikipedia.org)
  • Data obtained by using antibodies that detect specific isoforms of DMPK indicate that the most abundant isoform of DMPK is an 80-kDa protein expressed almost exclusively in smooth, skeletal, and cardiac muscles. (wikipedia.org)
  • Dystrophia myotonica protein kinase (DMPK) is a serine/threonine kinase composed of a kinase domain and a coiled-coil domain involved in the multimerization. (wikipedia.org)
  • In this model, transient activation of kinase activity would occur in response to G protein second messengers, while longterm activation of DMPK could be mediated by a membrane associated protease that cleaves DMPK-1 to release cytosolic DMPK-2 in a persistently activated form. (wikipedia.org)
  • Furthermore, we believe that these results could signal the potential for the accumulation of exon 51 skipped transcript and dystrophin protein in muscle tissue with repeated doses of PGN-EDO51 in people living with DMD. (tipranks.com)
  • Type 2 DM (DM2) is milder and involves a CCTG repeat expansion mutation of the cellular nucleic acid binding protein gene CNBP (previously known as ZFN9) on chromosome 3q21.3. (msdmanuals.com)
Allele1
  • If expression of a trait requires only one copy of a gene (one allele). (msdmanuals.com)
Chromosome2
  • Type 1 DM (DM1) involves expansion of a CTG trinucleotide repeat of the DMPK gene located on chromosome 19. (msdmanuals.com)
  • All homologous chromosome pairs contain two variant forms of the same gene , called " alleles ," which are passed down from parent to offspring. (amboss.com)
Proteins3
  • The close relationship of DMPK to the Rho-kinases has led to speculation whether DMPK activity may be regulated in vivo by small G proteins, particularly of the Rho family. (wikipedia.org)
  • DYNE-101 consists of an antigen-binding fragment antibody (Fab) conjugated to an antisense oligonucleotide (ASO) and is designed to enable targeted muscle tissue delivery with the goal of reducing toxic DMPK RNA in the nucleus, releasing splicing proteins, allowing normal mRNA processing and translation of normal proteins, and potentially stopping or reversing the disease. (tmcnet.com)
  • This expansion of CTG repeats causes toxic RNA to cluster in the nucleus, forming nuclear foci and altering the splicing of multiple proteins essential for normal cellular function. (tmcnet.com)
Disorders4
  • Autosomal Dominant Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. (msdmanuals.com)
  • Genetic disorders result from new or inherited gene mutations . (amboss.com)
  • Next-generation sequencing of the whole exome is useful for testing for multiple candidate genes simultaneously or for discovering new, rare disorders. (medlink.com)
  • Whole exome sequencing is not suitable for detecting polynucleotide repeat disorders or large insertion/deletions. (medlink.com)
Region3
  • The 3' untranslated region of this gene contains 5-37 copies of a CTG trinucleotide repeat. (wikipedia.org)
  • Repeat expansion is associated with condensation of local chromatin structure that disrupts the expression of genes in this region. (wikipedia.org)
  • It is a monogenic, autosomal dominant disease caused by an abnormal trinucleotide expansion in a region of the DMPK gene. (tmcnet.com)
Copies1
  • In a population of 250 individuals , there will be a total of 500 gene copies (all individuals carry two alleles of a gene ). (amboss.com)
Muscle1
  • In non-human primates, DYNE-101 demonstrated a favorable safety profile and achieved enhanced muscle distribution as evidenced by significant reduction in wild-type DMPK RNA. (tmcnet.com)
Human2
  • Dyne has generated comprehensive preclinical data supporting its DM1 program, including reduction of nuclear foci and correction of splicing in patient cells, robust knockdown of toxic human nuclear DMPK RNA and correction of splicing in a novel in vivo model developed by Dyne, and reversal of myotonia in a disease model. (tmcnet.com)
  • Human genetics is the study of the human genome and the transmission of genes from one generation to the next. (amboss.com)
Expression1
  • Epigenetic regulation of gene expression encompasses mechanisms that allow regulating the expression of the genes without modification of the DNA sequence. (amboss.com)
General1
  • Short-term activation of DMPK-1 and -2 may be mediated by transitory interaction with a small GTPase (G). A general model that accounts for DMPK oligomerization, processing, and regulation has been proposed. (wikipedia.org)
Structure1
  • The crystal structure of the kinase domain of DMPK bound to the inhibitor bisindolylmaleimide VIII (BIM-8) revealed a dimeric enzyme associated by a conserved dimerization domain. (wikipedia.org)
Dystrophia myoton3
  • Myotonin-protein kinase (MT-PK) also known as myotonic dystrophy protein kinase (MDPK) or dystrophia myotonica protein kinase (DMPK) is an enzyme that in humans is encoded by the DMPK gene. (wikipedia.org)
  • Dystrophia myotonica protein kinase (DMPK) is a serine/threonine kinase composed of a kinase domain and a coiled-coil domain involved in the multimerization. (wikipedia.org)
  • It was found that the triple nucleotide CTG repeat in the 3'-untranslated region (3'-UTR) of the dystrophia myotonica protein kinase (DMPK) gene was more than 100 times, and the diagnosis of DM1 was clear. (bvsalud.org)
Disorder2
  • These data demonstrate a robust reduction of toxic RNA foci, a hallmark of this repeat expansion disorder, in the nucleus as well as the correction of splicing and a significant reduction of myotonia with Cas13d and PUF constructs via different mechanisms of action," said John Leonard, Ph.D., chief scientific officer at Locanabio. (locanabio.com)
  • A familial disorder inherited as an autosomal dominant trait and characterized by the onset of progressive CHOREA and DEMENTIA in the fourth or fifth decade of life. (lookformedical.com)
Mutation1
Toxic3
  • The expanded CTG is transcribed into toxic CUG repeats in the DMPK RNA. (locanabio.com)
  • These toxic RNA repeats lead to disease symptoms including progressive muscle wasting, weakness and myotonia (delayed relaxation of skeletal muscle), a hallmark of DM1. (locanabio.com)
  • The disease mechanism for these untranslated repeats is called the "toxic RNA hypothesis. (medicalhomeportal.org)
Correlate1
  • Diseased people have the extended sequence that consists of 50 to several thousandCTG trinucleotides, and the severity of the clinical picture and the disease occurrence correlate with the size of the expansion. (paedcro.com)
Inhibitor2
  • The crystal structure of the kinase domain of DMPK bound to the inhibitor bisindolylmaleimide VIII (BIM-8) revealed a dimeric enzyme associated by a conserved dimerization domain. (wikipedia.org)
  • We have previously described the benefits of the correction of the GSK3ß-CUGBP1 pathway in DM1 mice (HSALR model) expressing 250 CUG repeats using the GSK3 inhibitor tideglusib (TG). (bvsalud.org)
Abnormal1
Enzyme1
  • However, the fibre type composition in skeletal muscle seemed somehow to affect DMPK decrease, as the lowest level of the enzyme was found in patients with the lowest content of type 1 fibre. (nih.gov)
Disease3
  • Despite cloning of the locus, the complex disease phenotype of DM has proven difficult to interpret, and the exact role of DMPK in the pathogenesis of DM remains unclear. (wikipedia.org)
  • The classification describes a continuum ranging from mild to severe disease, which generally correlates with trinucleotide repeat (CTG) length. (medicalhomeportal.org)
  • This disease isinherited in an autosomal dominant manner. (paedcro.com)
Mice2
  • Here, we show that TG treatments corrected the expression of ~17% of genes misregulated in DM1 mice, including genes involved in cell transport, development and differentiation. (bvsalud.org)
  • We found that correction of the GSK3ß-CUGBP1 pathway in mice expressing long CUG repeats (DMSXL model) is beneficial not only at the prenatal and postnatal stages, but also during adulthood. (bvsalud.org)
Genetic1
  • Autosomal Dominant Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. (msdmanuals.com)
Type1
Leads2
  • As the DMPK repeat is replicated, the hairpin loop that is formed leads to repeat expansion (a) or contractions (b). (wikipedia.org)
  • repeat expansion and RNA splicing dysregulation increases over time and leads to a gradual worsening in many domains including cognition, muscle strength, and others. (medicalhomeportal.org)
Model1
  • Short-term activation of DMPK-1 and -2 may be mediated by transitory interaction with a small GTPase (G). A general model that accounts for DMPK oligomerization, processing, and regulation has been proposed. (wikipedia.org)
Form1