Affinage

DMD

Dystrophin · UniProt P11532

Round 2 corrected
Length
3685 aa
Mass
426.8 kDa
Annotated
2026-04-28
130 papers in source corpus 14 papers cited in narrative 14 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Dystrophin is a large rod-shaped cytoskeletal protein that anchors the dystrophin-associated protein complex (DAPC) at the sarcolemma, mechanically linking the intracellular actin cytoskeleton to the extracellular basal lamina and scaffolding signaling molecules including nNOS and AQP4 (via syntrophin) to the membrane (PMID:3282674, PMID:7545544, PMID:11717465). Its modular architecture—an N-terminal actin-binding domain, 24 spectrin-like repeats with four proline-rich hinges, a cysteine-rich ZZ domain that binds β-dystroglycan, and a unique C-terminal domain—provides both structural rigidity and flexibility to the subsarcolemmal lattice (PMID:3282674, PMID:2407739, PMID:24302611). Loss-of-function mutations in the DMD gene cause Duchenne muscular dystrophy through DAPC destabilization, aberrant calcium handling involving RyR1 S-nitrosylation-dependent SR calcium leak and TRPC3 channel upregulation, and epigenetic silencing of the DMD locus itself via increased H3K9me3 (PMID:11917091, PMID:19198614, PMID:34930315, PMID:32616572). Premature termination codons in the gene reduce transcript levels through a transcriptional rather than nonsense-mediated decay mechanism, and this silencing is partially reversible by HDAC inhibition (PMID:32616572).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1987 High

    Identification of the causative gene for Duchenne muscular dystrophy resolved the molecular basis of the most common lethal X-linked myopathy, revealing a giant locus (~2000 kb) on Xp21 with concentrated deletions in affected patients.

    Evidence cDNA cloning and Southern blotting of 104 DMD patient samples

    PMID:3607877

    Open questions at the time
    • Protein product not yet characterized
    • Functional mechanism of pathology unknown
  2. 1988 High

    Determination of the full protein sequence and sarcolemmal localization established dystrophin as a rod-shaped membrane-associated cytoskeletal protein with homology to α-actinin and spectrin, directly explaining why its absence compromises membrane integrity.

    Evidence Full cDNA sequencing with domain analysis; immunofluorescence and Western blotting on normal and DMD muscle

    PMID:3282674 PMID:3287171

    Open questions at the time
    • Binding partners at the membrane unknown
    • Mechanism connecting membrane association to pathology unresolved
  3. 1990 High

    Refined mapping of the rod domain to 24 spectrin-like repeats and four proline-rich hinge regions provided a structural model explaining how dystrophin combines rigidity with flexibility at the sarcolemma.

    Evidence Sequence analysis of repeat units combined with limited proteolysis and Western blot mapping with five antisera

    PMID:2407739

    Open questions at the time
    • No atomic-resolution structure of a full repeat unit
    • Functional significance of individual hinges not tested
  4. 1995 High

    Discovery that nNOS is anchored to the sarcolemma through the dystrophin complex revealed a signaling scaffolding role beyond mechanical support, with selective loss of nNOS in mdx and DMD muscle linking dystrophin absence to aberrant nitric oxide signaling.

    Evidence Co-purification and membrane fractionation of nNOS with DAPC; loss of sarcolemmal nNOS in mdx mice and DMD patients

    PMID:7545544

    Open questions at the time
    • Precise binding interface within the DAPC not mapped
    • Downstream consequences of nNOS mislocalization not fully delineated
  5. 2001 High

    Demonstration that AQP4 polarization at perivascular astrocyte membranes depends on α-syntrophin (a DAPC component) extended dystrophin's scaffolding function to water channel localization in the CNS.

    Evidence Chemical cross-linking, co-IP from brain, immunogold EM, and α-syntrophin knockout mice

    PMID:11717465

    Open questions at the time
    • Direct dystrophin–syntrophin–AQP4 ternary complex not reconstituted in vitro
    • Functional consequence for brain water homeostasis in DMD patients not tested
  6. 2002 High

    Synthesis of biochemical and genetic evidence consolidated the DAPC model, establishing that dystrophin loss destabilizes the entire complex and activates calcium-dependent pathophysiological cascades.

    Evidence Comprehensive review integrating co-IP, transgenic/knockout mouse, and patient data

    PMID:11917091

    Open questions at the time
    • Specific calcium entry pathways not identified
    • Relative contributions of mechanical versus signaling deficits unclear
  7. 2009 High

    Identification of RyR1 S-nitrosylation and calstabin-1 depletion as a mechanism of SR calcium leak in mdx muscle provided a molecular explanation for calcium-driven muscle damage in dystrophin deficiency, and pharmacological rescue validated the pathway.

    Evidence Biochemical RyR1 isolation, S-nitrosylation assay, single-channel recording, and S107 rescue in mdx mice

    PMID:19198614

    Open questions at the time
    • Whether nNOS mislocalization is the sole source of aberrant S-nitrosylation not proven
    • Applicability to human DMD muscle not directly tested
  8. 2013 High

    Structure-function dissection of the ZZ domain showed that cysteine mutations cause protein misfolding while a β-dystroglycan-binding-deficient mutant retains subsarcolemmal localization, separating targeting from β-dystroglycan engagement.

    Evidence Engineered ZZ domain mutations in Dp71-like constructs with binding assays, expression, and localization studies

    PMID:24302611

    Open questions at the time
    • Studies used Dp71-based constructs rather than full-length dystrophin
    • Alternative targeting determinants not identified
  9. 2015 High

    Discovery that FUBP1 promotes DMD exon 39 inclusion via an intronic splicing enhancer revealed a layer of splicing regulation that controls dystrophin isoform expression.

    Evidence RNase-assisted pull-down/MS, RNA EMSA, RNA-ChIP, and minigene mutagenesis in human myoblasts

    PMID:25662218

    Open questions at the time
    • Physiological regulation of FUBP1 in muscle differentiation not explored
    • Impact on full-length dystrophin protein levels not measured
  10. 2019 Medium

    Characterization of sarcospan overexpression rescue in mdx hearts and TRPC3 upregulation in DMDmdx rats identified additional sarcolemmal factors—SSPN as a DAPC stabilizer and TRPC3 as a disease-relevant calcium entry channel—that modulate dystrophin-deficient pathology.

    Evidence SSPN transgenic overexpression with echocardiography and DAPC characterization in mdx mice; TRPC3 Western blot, calcium measurements, and Pyr10 pharmacological inhibition in DMDmdx rats

    PMID:31039133 PMID:34930315

    Open questions at the time
    • SSPN rescue findings from single lab and not independently replicated
    • TRPC3 mechanism not fully linked to specific dystrophin domain loss
    • Relative contribution of TRPC3 versus RyR1 leak to calcium overload unclear
  11. 2020 High

    The finding that premature termination codons in DMD silence the locus epigenetically (via H3K9me3) rather than through NMD revealed a feed-forward transcriptional silencing mechanism and identified HDAC inhibition as a potential intervention to restore transcript levels.

    Evidence NMD inhibition assay, in situ hybridization, nascent RNA-seq (TT-seq), ChIP for H3K9me3, and givinostat treatment in mdx mice

    PMID:32616572

    Open questions at the time
    • Writer/reader enzymes responsible for H3K9me3 deposition at DMD locus unknown
    • Whether epigenetic silencing occurs in human DMD muscle confirmed only indirectly

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic-resolution structure of full-length dystrophin within the DAPC, the relative contributions of mechanical instability versus signaling defects to disease progression, and the identity of the chromatin machinery that deposits repressive marks at the mutant DMD locus.
  • No cryo-EM or crystallographic structure of full-length dystrophin in complex
  • Mechanistic separation of scaffolding versus signaling roles in vivo not achieved
  • Epigenetic silencing pathway at DMD locus not fully mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0008092 cytoskeletal protein binding 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005856 cytoskeleton 3
Pathway
R-HSA-1643685 Disease 3 R-HSA-397014 Muscle contraction 3 GO:0005886 plasma membrane 1
Partners
AQP4DAG1FUBP1NOS1SGCASNTA1SSPN
Complex memberships
Dystrophin-associated protein complex (DAPC)

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1987 The DMD cDNA (14 kb) was fully cloned and the dystrophin gene was shown to be organized into at least 60 exons spanning ~2000 kb on Xp21; deletions concentrated in a specific genomic segment were identified in 53/104 DMD patients. cDNA cloning, Southern blotting, genomic mapping Cell High 3607877
1988 The complete dystrophin protein sequence (3685 aa) was determined, revealing four structural domains: an N-terminal actin-binding domain conserved with α-actinin, a large rod domain of 25 spectrin-like triple-helical repeats, a cysteine-rich domain similar to Dictyostelium α-actinin, and a unique C-terminal domain; the protein is predicted to adopt a rod shape ~150 nm long. Full cDNA sequencing and protein sequence analysis with domain comparison Cell High 3282674
1988 Dystrophin protein is localized to the sarcolemma of normal human skeletal muscle and is reduced or absent in DMD patients; antibodies to N-terminal peptides identify a ~400 kDa sarcolemmal protein, indicating dystrophin anchors cytoskeletal elements to the surface membrane. Immunofluorescence on muscle cryosections, Western blotting with anti-peptide antibodies Nature High 3287171
1990 Detailed analysis of the dystrophin repeat domain revealed 24 spectrin-like repeat units (not 26) with four proline-rich non-repeat spacers (hinge segments) sensitive to proteolysis, proposing a model in which hinges confer flexibility to a membrane-associated dystrophin network. Sequence analysis of repeat units; limited proteolysis with five anti-dystrophin antisera detecting fragments by Western blot The Journal of biological chemistry High 2407739
1995 Neuronal NOS (nNOS) is localized to the sarcolemma of fast-twitch skeletal muscle fibers through direct association with the dystrophin complex via an N-terminal GLGF-motif-containing domain of nNOS; mdx mice and DMD patients show selective loss of nNOS from muscle membranes, indicating dystrophin is required for sarcolemmal localization of this signaling enzyme. Co-purification, membrane fractionation, nNOS activity assay, immunostaining in mdx and DMD muscle Cell High 7545544
2002 Dystrophin is located at the muscle sarcolemma within a membrane-spanning protein complex (dystrophin-associated protein complex, DAPC) that connects the intracellular actin cytoskeleton to the extracellular basal lamina; loss of dystrophin destabilizes this complex and activates pathophysiological processes including altered intracellular calcium handling. Review synthesizing biochemical fractionation, co-immunoprecipitation, transgenic/knockout mouse studies, and patient data Physiological reviews High 11917091
2001 Aquaporin-4 (AQP4) is tethered to perivascular astrocyte endfeet membranes through binding of its C-terminal PDZ-binding motif to the PDZ domain of alpha-syntrophin, a component of the dystrophin protein complex; in alpha-syntrophin knockout mice, AQP4 loses its polarized localization at blood vessel-facing membranes, and its stability is reduced. Chemical cross-linking, co-immunoprecipitation from brain, high-resolution immunogold EM, alpha-Syn-/- mice, pulse-chase labeling, transfected cell lines with C-terminal deletion Proceedings of the National Academy of Sciences of the United States of America High 11717465
2009 In mdx dystrophic skeletal muscle, RyR1 (ryanodine receptor) undergoes age-dependent S-nitrosylation, which depletes the channel-stabilizing protein FKBP12/calstabin-1 from the complex, producing 'leaky' sarcoplasmic reticulum Ca2+ release channels; preventing calstabin-1 depletion with compound S107 reduces SR Ca2+ leak, muscle damage, and improves exercise performance in mdx mice. Biochemical isolation of RyR1 from mdx muscle, S-nitrosylation assay, calstabin-1 binding assay, single-channel recording, pharmacological rescue with S107, histology and exercise testing in mdx mice Nature medicine High 19198614
2013 Missense mutations in the ZZ domain of dystrophin cause disease through two distinct pathogenic mechanisms: cysteine mutations (p.Cys3313Phe, p.Cys3340Tyr) produce protein instability/misfolding and loss of subsarcolemmal expression, whereas an aspartic acid mutation (p.Asp3335His) disrupts binding to β-dystroglycan while leaving subsarcolemmal localization largely intact, demonstrating that β-dystroglycan binding is not required for subsarcolemmal targeting. Engineering ZZ mutations into Dp71-like constructs, in vitro binding assays, cell transfection, protein expression and localization studies, in vivo studies Human mutation High 24302611
2015 FUSE binding protein 1 (FUBP1) promotes inclusion of DMD exon 39 in mature transcripts by binding to an intronic splicing enhancer (ISE) in intron 38; this was demonstrated by RNase-assisted pull-down coupled with mass spectrometry, RNA EMSA, RNA-ChIP on endogenous DMD pre-mRNA, and minigene mutagenesis studies in human myoblasts. RNase-assisted pull-down + mass spectrometry, RNA EMSA, RNA-ChIP, minigene serial deletion and mutagenesis, transfection in human myoblast cell line Nucleic acids research High 25662218
2020 Premature termination codons (PTCs) in the DMD gene reduce local DMD mRNA synthesis through a transcriptional/epigenetic mechanism rather than nonsense-mediated decay (NMD): NMD inhibition does not rescue mRNA levels; in situ hybridization shows DMD mRNA is predominantly nuclear; nascent RNA sequencing reveals lower transcription rate in patient myotubes; ChIP shows increased repressive H3K9me3 marks at the DMD locus in mdx mice; HDAC inhibitor givinostat increases DMD transcript levels. NMD inhibition assay, in situ hybridization, nascent RNA sequencing (TT-seq), chromatin immunoprecipitation (ChIP), pharmacological HDAC inhibition in mdx mice Proceedings of the National Academy of Sciences of the United States of America High 32616572
2019 In DMD cardiomyocytes, disease-state exosomes (DMD-exo) contain altered microRNA cargo (affecting p53 and TGF-beta pathways) and promote vulnerability to oxidative stress, mitochondrial membrane potential loss, and cell death, whereas non-affected exosomes are cardioprotective; inhibition of DMD-exo secretion in vitro and in vivo improves stress responses. iPSC-derived cardiomyocytes (DMD-iCMs), exosome isolation, miRNA profiling, reactive oxygen species assay, mitochondrial membrane potential assay, cell death assay, exosome surface peptide profiling, transcriptomic profiling, in vivo exosome secretion inhibition Disease models & mechanisms Medium 33188007
2019 Sarcospan (SSPN) interacts with dystrophin and utrophin at the sarcolemma; SSPN overexpression in mdx mice restores cardiac sarcolemmal stability, enhances fully glycosylated α-dystroglycan abundance, improves systolic function, reduces fibrosis, and partially restores β-adrenergic responsiveness, demonstrating SSPN as a membrane-stabilizing component of the DAPC. Transgenic overexpression in mdx and mdx:utr-haploinsufficient mice, echocardiography, hemodynamic pressure-volume measurements, immunostaining, Western blotting for DAPC components JCI insight Medium 31039133
2021 In DMDmdx rats, TRPC3 calcium channel protein levels are elevated as early as 1.5 months of age and contribute to increased sarcolemmal calcium permeability; pharmacological inhibition of TRPC3 with Pyr10 abolishes the elevated sarcoplasmic calcium permeability in DMDmdx muscle fibers, and rAAV-microdystrophin treatment only partially normalizes TRPC3 levels and calcium homeostasis. RT-qPCR, Western blot, immunocytofluorescence, cytosolic [Ca2+] measurement, sarcolemmal permeability assay, pharmacological inhibition (Pyr10), rAAV-microdystrophin gene therapy in DMDmdx rats Journal of translational medicine Medium 34930315

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1987 Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell 2115 3607877
2019 Blood-Brain Barrier: From Physiology to Disease and Back. Physiological reviews 1645 30280653
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1988 The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell 1429 3282674
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
1986 Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene. Nature 932 3773991
1988 Deletion screening of the Duchenne muscular dystrophy locus via multiplex DNA amplification. Nucleic acids research 923 3205741
2002 Function and genetics of dystrophin and dystrophin-related proteins in muscle. Physiological reviews 899 11917091
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2003 Dystrophin and mutations: one gene, several proteins, multiple phenotypes. The Lancet. Neurology 829 14636778
1995 Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy. Cell 826 7545544
2005 The DNA sequence of the human X chromosome. Nature 816 15772651
2000 DNA cloning using in vitro site-specific recombination. Genome research 815 11076863
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1990 Detection of 98% of DMD/BMD gene deletions by polymerase chain reaction. Human genetics 630 2253937
1988 The Duchenne muscular dystrophy gene product is localized in sarcolemma of human skeletal muscle. Nature 620 3287171
2015 Widespread macromolecular interaction perturbations in human genetic disorders. Cell 454 25910212
2009 Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle. Nature medicine 424 19198614
2016 Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. Cell 423 26871637
2001 Syntrophin-dependent expression and localization of Aquaporin-4 water channel protein. Proceedings of the National Academy of Sciences of the United States of America 413 11717465
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2007 Functional specialization of beta-arrestin interactions revealed by proteomic analysis. Proceedings of the National Academy of Sciences of the United States of America 360 17620599
2006 Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia. Molecular psychiatry 345 17043677
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
1990 Detailed analysis of the repeat domain of dystrophin reveals four potential hinge segments that may confer flexibility. The Journal of biological chemistry 338 2407739
2004 Decreased BMD and limb deformities in mice carrying mutations in both Lrp5 and Lrp6. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 282 15537447
1989 Molecular and phenotypic analysis of patients with deletions within the deletion-rich region of the Duchenne muscular dystrophy (DMD) gene. American journal of human genetics 176 2491010
2011 Current status of pharmaceutical and genetic therapeutic approaches to treat DMD. Molecular therapy : the journal of the American Society of Gene Therapy 149 21468001
2005 Deletion and duplication screening in the DMD gene using MLPA. European journal of human genetics : EJHG 139 16030524
2006 Duplications in the DMD gene. Human mutation 120 16917894
2010 Clinical and genetic characterization of manifesting carriers of DMD mutations. Neuromuscular disorders : NMD 118 20630757
1984 Duchenne muscular dystrophy involving translocation of the dmd gene next to ribosomal RNA genes. Science (New York, N.Y.) 115 6729462
2018 Humanizing the mdx mouse model of DMD: the long and the short of it. NPJ Regenerative medicine 107 29479480
2004 Antagonism between DNA hypermethylation and enhancer-blocking activity at the H19 DMD is uncovered by CpG mutations. Nature genetics 95 15273688
2019 Canine osteosarcoma genome sequencing identifies recurrent mutations in DMD and the histone methyltransferase gene SETD2. Communications biology 85 31341965
2011 Regulation of DMD pathology by an ankyrin-encoded miRNA. Skeletal muscle 84 21824387
2007 Generation and characterization of transgenic mice with the full-length human DMD gene. The Journal of biological chemistry 73 18083704
2006 Copy number variation in the genome; the human DMD gene as an example. Cytogenetic and genome research 69 17124406
2015 Second-generation compound for the modulation of utrophin in the therapy of DMD. Human molecular genetics 66 25935002
2007 Optimizing exon skipping therapies for DMD. Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology 62 18646569
1998 Dmd(mdx-beta geo): a new allele for the mouse dystrophin gene. Developmental dynamics : an official publication of the American Association of Anatomists 56 9626497
2020 Premature termination codons in the DMD gene cause reduced local mRNA synthesis. Proceedings of the National Academy of Sciences of the United States of America 55 32616572
2013 Symptomatic female carriers of Duchenne muscular dystrophy (DMD): genetic and clinical characterization. Journal of the neurological sciences 51 24135430
2006 COL1A1, ESR1, VDR and TGFB1 polymorphisms and haplotypes in relation to BMD in Spanish postmenopausal women. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 51 17021946
2004 Recombinant adeno-associated viral (rAAV) vectors as therapeutic tools for Duchenne muscular dystrophy (DMD). Gene therapy 51 15454965
2019 Relationships between DMD mutations and neurodevelopment in dystrophinopathy. Neurology 50 31594858
2004 Association between exercise and pubertal BMD is modulated by estrogen receptor alpha genotype. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 50 15476574
2018 Skipping Multiple Exons to Treat DMD-Promises and Challenges. Biomedicines 49 29301272
2015 Clinical features of patients with dystrophinopathy sharing the 45-55 exon deletion of DMD gene. Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology 47 26155064
2012 LINC complex alterations in DMD and EDMD/CMT fibroblasts. European journal of cell biology 47 22555292
2021 Systems genetics in diversity outbred mice inform BMD GWAS and identify determinants of bone strength. Nature communications 45 34099702
2021 The DMD gene and therapeutic approaches to restore dystrophin. Neuromuscular disorders : NMD 45 34736624
2015 Impact of Genomics Platform and Statistical Filtering on Transcriptional Benchmark Doses (BMD) and Multiple Approaches for Selection of Chemical Point of Departure (PoD). PloS one 43 26313361
2021 Pharmacology and toxicology of eteplirsen and SRP-5051 for DMD exon 51 skipping: an update. Archives of toxicology 42 34797383
2004 Rapid identification of female carriers of DMD/BMD by quantitative real-time PCR. Human mutation 42 15024733
2016 Endogenous Multiple Exon Skipping and Back-Splicing at the DMD Mutation Hotspot. International journal of molecular sciences 41 27754374
2013 Interplay between DMD point mutations and splicing signals in Dystrophinopathy phenotypes. PloS one 41 23536893
2007 Identification of mouse Duffy antigen receptor for chemokines (Darc) as a BMD QTL gene. Genome research 41 17416748
2000 Association of CTR and COLIA1 alleles with BMD values in peri- and postmenopausal women. Calcified tissue international 41 11136533
2017 Normal and altered pre-mRNA processing in the DMD gene. Human genetics 39 28597072
2023 Myopathologic trajectory in Duchenne muscular dystrophy (DMD) reveals lack of regeneration due to senescence in satellite cells. Acta neuropathologica communications 35 37858263
2019 Exons 45-55 Skipping Using Mutation-Tailored Cocktails of Antisense Morpholinos in the DMD Gene. Molecular therapy : the journal of the American Society of Gene Therapy 35 31416775
1989 Hot spot of recombination within DXS164 in the Duchenne muscular dystrophy gene. American journal of human genetics 34 2570527
2020 Exon skipping induced by nonsense/frameshift mutations in DMD gene results in Becker muscular dystrophy. Human genetics 33 31919629
2010 Use of multiplex ligation-dependent probe amplification (MLPA) for Duchenne muscular dystrophy (DMD) gene mutation analysis. The Indian journal of medical research 33 20847377
2011 Immune response and mitochondrial metabolism are commonly deregulated in DMD and aging skeletal muscle. PloS one 31 22096509
2017 Non-myogenic tumors display altered expression of dystrophin (DMD) and a high frequency of genetic alterations. Oncotarget 30 27391342
2015 FUBP1: a new protagonist in splicing regulation of the DMD gene. Nucleic acids research 30 25662218
1987 Familial inheritance of a DXS164 deletion mutation from a heterozygous female. American journal of human genetics 30 2887110
2020 Common therapeutic advances for Duchenne muscular dystrophy (DMD). The International journal of neuroscience 29 32241218
2009 Association of the aromatase gene alleles with BMD: epidemiological and functional evidence. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 29 19419293
2020 Pseudoexons of the DMD Gene. Journal of neuromuscular diseases 28 32176650
2019 Current and emerging therapies in Becker muscular dystrophy (BMD). Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology 27 31788661
2014 When a mid-intronic variation of DMD gene creates an ESE site. Neuromuscular disorders : NMD 27 25193336
2008 Similarity of DMD gene deletion and duplication in the Chinese patients compared to global populations. Behavioral and brain functions : BBF 26 18445268
2022 Prime editing optimized RTT permits the correction of the c.8713C>T mutation in DMD gene. Molecular therapy. Nucleic acids 24 36320324
2020 Duchenne muscular dystrophy (DMD) cardiomyocyte-secreted exosomes promote the pathogenesis of DMD-associated cardiomyopathy. Disease models & mechanisms 24 33188007
2019 Stabilization of the cardiac sarcolemma by sarcospan rescues DMD-associated cardiomyopathy. JCI insight 24 31039133
2019 Exonic rearrangements in DMD in Chinese Han individuals affected with Duchenne and Becker muscular dystrophies. Human mutation 24 31705731
2015 Dietary MicroRNA Database (DMD): An Archive Database and Analytic Tool for Food-Borne microRNAs. PloS one 23 26030752
2018 Anxa2 attenuates osteoblast growth and is associated with hip BMD and osteoporotic fracture in Chinese elderly. PloS one 22 29570731
2015 Integrative Analysis of Transcriptomic and Epigenomic Data to Reveal Regulation Patterns for BMD Variation. PloS one 22 26390436
2008 Clinical approaches in the treatment of Duchenne muscular dystrophy (DMD) using oligonucleotides. Frontiers in bioscience : a journal and virtual library 22 17981565
2013 The ZZ domain of dystrophin in DMD: making sense of missense mutations. Human mutation 21 24302611
2002 Gene transfer studies in animals: what do they really tell us about the prospects for gene therapy in DMD? Neuromuscular disorders : NMD 21 12206790
2020 Clinical Phenotypes of DMD Exon 51 Skip Equivalent Deletions: A Systematic Review. Journal of neuromuscular diseases 20 32417793
2019 Genotypes and Phenotypes of DMD Small Mutations in Chinese Patients With Dystrophinopathies. Frontiers in genetics 20 30833962
2022 Current Practices in Treating Cardiomyopathy and Heart Failure in Duchenne Muscular Dystrophy (DMD): Understanding Care Practices in Order to Optimize DMD Heart Failure Through ACTION. Pediatric cardiology 19 35024902
2022 Cardiac care of children with dystrophinopathy and females carrying DMD-gene variations. Open heart 19 36252992
2019 The SINE Compound KPT-350 Blocks Dystrophic Pathologies in DMD Zebrafish and Mice. Molecular therapy : the journal of the American Society of Gene Therapy 19 31628052
2024 The complex landscape of DMD mutations: moving towards personalized medicine. Frontiers in genetics 18 38596212
2016 The emerging role of viral vectors as vehicles for DMD gene editing. Genome medicine 18 27215286
2016 Characterization of a Dmd (EGFP) reporter mouse as a tool to investigate dystrophin expression. Skeletal muscle 18 27382459
2009 Validation and comparison of two quantitative real-time PCR assays for direct detection of DMD/BMD carriers. Clinical biochemistry 18 19439162
2005 Localized expression of specific P2X receptors in dystrophin-deficient DMD and mdx muscle. Neuromuscular disorders : NMD 18 15725584
2022 Detection of pericentric inversion with breakpoint in DMD by whole genome sequencing. Molecular genetics & genomic medicine 17 35912688
2016 Structural characterizations of phage antitoxin Dmd and its interactions with bacterial toxin RnlA. Biochemical and biophysical research communications 16 26972252
2015 Adeno-Associated Virus (AAV) Mediated Dystrophin Gene Transfer Studies and Exon Skipping Strategies for Duchenne Muscular Dystrophy (DMD). Current gene therapy 16 26159373
2014 Is GSN significant for hip BMD in female Caucasians? Bone 16 24607942
2009 Characterization of the DMD/BMD patient population in Czech Republic and Slovakia using an innovative registry approach. Neuromuscular disorders : NMD 16 19269824
2009 Point mutations in Czech DMD/BMD patients and their phenotypic outcome. Neuromuscular disorders : NMD 16 19783145
2024 Comparison of pharmaceutical properties and biological activities of prednisolone, deflazacort, and vamorolone in DMD disease models. Human molecular genetics 15 37819629
2022 Reclassification of DMD Duplications as Benign: Recommendations for Cautious Interpretation of Variants Identified in Prenatal Screening. Genes 15 36360209
2016 Association of ACTN3 polymorphisms with BMD, and physical fitness of elderly women. Journal of physical therapy science 15 27821924
2021 Pathological alterations in the gastrointestinal tract of a porcine model of DMD. Cell & bioscience 14 34266495
2021 TRPC3, but not TRPC1, as a good therapeutic target for standalone or complementary treatment of DMD. Journal of translational medicine 14 34930315
2019 Targeted sequencing of the DMD locus: A comprehensive diagnostic tool for all mutations. The Indian journal of medical research 14 31719299
2018 High urinary ferritin reflects myoglobin iron evacuation in DMD patients. Neuromuscular disorders : NMD 14 29776718
2023 DMD-Associated Dilated Cardiomyopathy: Genotypes, Phenotypes, and Phenocopies. Circulation. Genomic and precision medicine 13 37671549
2020 Ethnicity-related DMD Genotype Landscapes in European and Non-European Countries. Neurology. Genetics 13 33376799
2001 Point mutation and polymorphism in Duchenne/Becker muscular dystrophy (D/BMD) patients. Experimental & molecular medicine 13 11795488
2022 Dystrophinopathy Phenotypes and Modifying Factors in DMD Exon 45-55 Deletion. Annals of neurology 12 35897138
2016 Comparative transcriptome analysis of muscular dystrophy models Large(myd), Dmd(mdx)/Large(myd) and Dmd(mdx): what makes them different? European journal of human genetics : EJHG 12 26932192
2014 Associations between Body Composition, Hormonal and Lifestyle Factors, Bone Turnover, and BMD. Journal of bone metabolism 12 24707468
2008 Sex-specific association of the glucocorticoid receptor gene with extreme BMD. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 12 17937535
1993 Screening of deletions and RFLP analysis in Turkish DMD/BMD families by PCR. Clinical genetics 12 8104108
2024 Severe cardiac and skeletal manifestations in DMD-edited microminipigs: an advanced surrogate for Duchenne muscular dystrophy. Communications biology 11 38702481
2022 Identification of Known and Novel Long Noncoding RNAs Potentially Responsible for the Effects of Bone Mineral Density (BMD) Genomewide Association Study (GWAS) Loci. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 11 35695880
2022 Clinical, muscle imaging, and genetic characteristics of dystrophinopathies with deep-intronic DMD variants. Journal of neurology 11 36319768
2019 Breakpoint junction features of seven DMD deletion mutations. Human genome variation 11 31645977
2018 Pulmonary function and clinical correlation in DMD. Paediatric respiratory reviews 11 31130422
2014 MLPA Application in Clinical Diagnosis of DMD/BMD in Shanghai. Journal of clinical laboratory analysis 11 25131993
2000 Screening of dystrophin gene deletions in Egyptian patients with DMD/BMD muscular dystrophies. Disease markers 11 11381192
2022 Molecular Fingerprint of BMD Patients Lacking a Portion in the Rod Domain of Dystrophin. International journal of molecular sciences 10 35269765