Genomes and Genes
Gene Symbol: DOK7
Description: docking protein 7
Alias: C4orf25, CMS10, CMS1B, protein Dok-7, downstream of tyrosine kinase 7
- Clinical and molecular genetic findings in COLQ-mutant congenital myasthenic syndromesVioleta Mihaylova
Friedrich Baur Institute, Department of Neurology, Ludwig Maximilians University, Munich, Germany
Brain 131:747-59. 2008..many patients had clinical features reminiscent of limb-girdle CMS with mutations in the recently discovered DOK7 gene, including sparing of eye movements and a predominantly proximal muscle weakness...
- Congenital myasthenic syndromes and the formation of the neuromuscular junctionDavid Beeson
Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK
Ann N Y Acad Sci 1132:99-103. 2008..Dok-7 binds MuSK and many of the mutations of DOK7 impair the MuSK signaling pathway...
- Phenotype genotype analysis in 15 patients presenting a congenital myasthenic syndrome due to mutations in DOK7A Ben Ammar
Institut National de Neurologie, Universite Tunis El Manar, Tunis, Tunisia
J Neurol 257:754-66. 2010..Mutations of DOK7 have recently been described in recessive forms of CMS...
- Identification of previously unreported mutations in CHRNA1, CHRNE and RAPSN genes in three unrelated Italian patients with congenital myasthenic syndromesRaffaella Brugnoni
Laboratory NBS Biotech, Fondazione Istituto Neurologico Carlo Besta, Milan, Italy
J Neurol 257:1119-23. 2010..The alphaG378D mutation was recessive, but recessive CHRNA1 mutations have rarely been reported previously, so studies on the effect of this mutation at the cellular level would be of interest...
- Dok-7 mutations underlie a neuromuscular junction synaptopathyDavid Beeson
Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK
Science 313:1975-8. 2006..We showed that recessive inheritance of mutations in Dok-7, which result in a defective structure of the neuromuscular junction, is a cause of CMS with proximal muscle weakness...
- The cytoplasmic adaptor protein Dok7 activates the receptor tyrosine kinase MuSK via dimerizationElisa Bergamin
Structural Biology Program, Kimmel Center for Biology and Medicine of the Skirball Institute and Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
Mol Cell 39:100-9. 2010..and the following muscle proteins: LRP4, the receptor for Agrin; MuSK, a receptor tyrosine kinase (RTK); and Dok7 (or Dok-7), a cytoplasmic adaptor protein...
- Variable phenotypes associated with mutations in DOK7Jennifer A Anderson
Department of Neurology, University of California at Davis, Davis, CA 95618, USA
Muscle Nerve 37:448-56. 2008..with the limb-girdle variant of congenital myasthenic syndrome (CMS) possess mutations in the human Dok-7 gene (DOK7). We identified six unrelated CMS patients with DOK7 mutations...
- The muscle protein Dok-7 is essential for neuromuscular synaptogenesisKumiko Okada
Department of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113 8510, Japan
Science 312:1802-5. 2006..Mice lacking Dok-7 formed neither acetylcholine receptor clusters nor neuromuscular synapses. Thus, Dok-7 is essential for neuromuscular synaptogenesis through its interaction with MuSK...
- Phenotypical spectrum of DOK7 mutations in congenital myasthenic syndromesJuliane S Muller
Friedrich Baur Institute, Department of Neurology, Ludwig Maximilians University, Munich, Germany
Brain 130:1497-506. 2007..Subsequently, we and others identified mutations in DOK7 as a cause of congenital myasthenic syndromes (CMS), providing evidence for a crucial role of Dok-7 in maintaining ..
- Clinical features of the DOK7 neuromuscular junction synaptopathyJacqueline Palace
Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS, UK
Brain 130:1507-15. 2007Mutations in DOK7 have recently been shown to underlie a recessive congenital myasthenic syndrome (CMS) associated with small simplified neuromuscular junctions ('synaptopathy') but normal acetylcholine receptor and acetylcholinesterase ..
- Dok-7 myasthenia: phenotypic and molecular genetic studies in 16 patientsDuygu Selcen
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA
Ann Neurol 64:71-87. 2008..Detailed analysis of phenotypic and molecular genetic aspects of Dok-7 myasthenia in 16 patients...
- The carboxyl-terminal region of Dok-7 plays a key, but not essential, role in activation of muscle-specific receptor kinase MuSK and neuromuscular synapse formationRyo Ueta
Division of Genetics, Department of Cancer Biology
J Biochem . 2017..Dok-7 is the essential cytoplasmic activator of MuSK, and indeed mice lacking Dok-7 form no NMJs. Moreover, DOK7 gene mutations underlie DOK7 myasthenia, an NMJ synaptopathy...
- Prenatal diagnosis and genetic analysis of fetal akinesia deformation sequence and multiple pterygium syndrome associated with neuromuscular junction disorders: a reviewChih Ping Chen
Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
Taiwan J Obstet Gynecol 51:12-7. 2012..Genetic analysis of mutations in the neuromuscular junction genes such as CHRNA1, CHRND, CHRNG, CNTN1, DOK7, RAPSN, and SYNE1 may unveil the pathogenetic cause of fetal akinesia deformation sequence and multiple pterygium ..
- Salbutamol-responsive limb-girdle congenital myasthenic syndrome due to a novel missense mutation and heteroallelic deletion in MUSKConstanze Gallenmüller
Friedrich Baur Institut, Ludwig Maximilians University, Munich, Germany
Neuromuscul Disord 24:31-5. 2014..Our findings highlight the importance of a molecular diagnosis in CMS and demonstrate considerable similarities between patients with MUSK and DOK7-related CMS in terms of clinical phenotype and treatment options.
- LRP4 third β-propeller domain mutations cause novel congenital myasthenia by compromising agrin-mediated MuSK signaling in a position-specific mannerBisei Ohkawara
Division of Neurogenetics, Center for Neurological Diseases and Cancer and
Hum Mol Genet 23:1856-68. 2014..We conclude that LRP4 is a new CMS disease gene and that the 3rd beta propeller domain of LRP4 mediates the two signaling pathways in a position-specific manner. ..
- Pharmacologic treatment of downstream of tyrosine kinase 7 congenital myasthenic syndromeNanna Witting
Neuromuscular Research Unit, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
JAMA Neurol 71:350-4. 2014..Congenital myasthenic syndromes (CMSs) are increasingly recognized as causes of muscle fatigue and weakness. However, treatment of individual syndromes has been described only in small case series...
- Identification of a Dutch founder mutation in MUSK causing fetal akinesia deformation sequenceM Brigita Tan-Sindhunata
Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands
Eur J Hum Genet 23:1151-7. 2015..FADS can result from mutations in CHRNG, CHRNA1, CHRND, DOK7 and RAPSN; however, these genes only account for a minority of cases...
- Exercise training alters DNA methylation patterns in genes related to muscle growth and differentiation in miceTimo Kanzleiter
Department of Experimental Diabetology, German Institute of Human Nutrition, Potsdam Rehbruecke, Germany German Center for Diabetes Research DZD, Neuherberg, Germany and
Am J Physiol Endocrinol Metab 308:E912-20. 2015..factors (Plexin A2) as well as genes that participate in muscle hypertrophy (Igfbp4) and motor neuron innervation (Dok7)...
- Limb girdle weakness responding to salbutamol: an Indian family with DOK7 mutationS Khadilkar
Department of Neurology, Grant Government Medical College and JJ Hospital, Mumbai, India and Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Atlanta, Georgia, 30322, USA Correspondence to Prof Satish Khadilkar, 110, New Wing, First Floor, Bombay Hospital, 12, New Marine Lines, Mumbai 400 020, India
Indian Pediatr 52:243-4. 2015..Congenital Myasthenic Syndromes (CMS) are heterogeneous genetic diseases...
- DNA methylation as a promising landscape: A simple blood test for breast cancer predictionGolnaz Khakpour
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Tumour Biol 36:4905-12. 2015..for predisposition to breast cancer, leading to suggest that ATM, TITF1, SFRP1, NUP155, NEUROD1, ZNF217, DBC2, DOK7 and ESR1 genes and the LINE1, Alu and Sat2 DNA elements could be considered as the potential epimarkers...
- Protein kinase CK2 interacts at the neuromuscular synapse with Rapsyn, Rac1, 14-3-3γ, and Dok-7 proteins and phosphorylates the latter twoDustin Herrmann
From the Institut für Biochemie, Friedrich Alexander Universitat Erlangen Nurnberg, Fahrstrasse 17, D 91054 Erlangen, Germany
J Biol Chem 290:22370-84. 2015..Additionally, we mapped the interacting epitopes of all four binding partners to CK2 and thereby gained insights into the potential role of the CK2/Rapsyn interaction. ..
- Global N-linked Glycosylation is Not Significantly Impaired in Myoblasts in Congenital Myasthenic Syndromes Caused by Defective Glutamine-Fructose-6-Phosphate Transaminase 1 (GFPT1)Qiushi Chen
Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
Biomolecules 5:2758-81. 2015..controls, three GFPT1 patients, and four patients with other muscular diseases, namely CMS caused by mutations in DOK7, myopathy caused by mutations in MTND5, limb girdle muscular dystrophy type 2A (LGMD2A), and Pompe disease...
- Effective Treatment With Albuterol in DOK7 Congenital Myasthenic Syndrome in ChildrenChang Yong Tsao
Nationwide Children s Hospital, The Ohio State University, Columbus, Ohio Electronic address
Pediatr Neurol 54:85-7. 2016..DOK7 (downstream of tyrosine kinase 7) congenital myasthenic syndrome was previously treated successfully with ephedrine and salbutamol; ..
- Anticholinesterase Therapy Worsening Head Drop and Limb Weakness Due to a Novel DOK7 MutationDominika Lozowska
Department of Neurology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO Prevention Genetics, Marshfield, WI and Invitae Corporation, San Francisco, CA
J Clin Neuromuscul Dis 17:72-7. 2015Dok-7 myasthenia is an autosomal recessive congenital myasthenic syndrome due to DOK7 mutations...
- Congenital Myasthenic Syndromes with Predominant Limb Girdle WeaknessTeresinha Evangelista
John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular Diseases, Newcastle University, Newcastle upon Tyne, UK
J Neuromuscul Dis 2:S21-S29. 2015..LG-CMS are inherited in autosomal recessive traits, and are often associated with mutations in DOK7 and GFPT1, and less frequently with mutations in COLQ, ALG2, ALG14 and DPAGT...
- Postnatal knockdown of dok-7 gene expression in mice causes structural defects in neuromuscular synapses and myasthenic pathologyTakahiro Eguchi
Division of Genetics, Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, 108 8639, Japan
Genes Cells 21:670-6. 2016..Indeed, mice lacking either Dok-7 or MuSK form no NMJs, and defects in the human DOK7 gene underlie a congenital myasthenic syndrome (an NMJ disorder)...
- Multiscale Simulations Suggest a Mechanism for the Association of the Dok7 PH Domain with PIP-Containing MembranesAmanda Buyan
Department of Biochemistry, University of Oxford, Oxford, United Kingdom
PLoS Comput Biol 12:e1005028. 2016b>Dok7 is a peripheral membrane protein that is associated with the MuSK receptor tyrosine kinase. Formation of the Dok7/MuSK/membrane complex is required for the activation of MuSK...
- Silencing of Dok-7 in Adult Rat Muscle Increases Susceptibility to Passive Transfer Myasthenia GravisAlejandro M Gomez
Neuroimmunology Group, Division of Neuroscience, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands Electronic address
Am J Pathol 186:2559-68. 2016..These results suggest that a reduced expression of Dok-7 may play a role in the susceptibility to passive transfer MG, by rendering AChR clusters less resistant to the autoantibody attack. ..
- Congenital myasthenic syndrome in Israel: Genetic and clinical characterizationSharon Aharoni
Institute of Child Neurology, Schneider Children s Medical Center of Israel, Petach Tikva, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Electronic address
Neuromuscul Disord . 2016..Mutations in CHRNE were identified in 7 kinships. Less commonly detected mutations were in CHRND, CHAT, GFPT1 and DOK7. In conclusion, mutations in RAPSN and COLQ are the most common causes of CMS in our cohort...
- Divalent and monovalent autoantibodies cause dysfunction of MuSK by distinct mechanisms in a rabbit model of myasthenia gravisShuuichi Mori
Department of Geriatric Medicine, Tokyo Metropolitan Institute of Gerontology, Tokyo 173 0015, Japan
J Neuroimmunol 244:1-7. 2012..Taken together, these findings suggest that complement activation is not necessary for the MG onset and that both divalent and monovalent antibodies may cause MG in vivo by inducing MuSK dysfunction...
- A mutation causes MuSK reduced sensitivity to agrin and congenital myastheniaAsma Ben Ammar
INSERM, UMRS 975, UPMC, institut du cerveau et de la moelle épinière, Groupe Hospitalier Pitie Salpetriere, Paris, France
PLoS ONE 8:e53826. 2013..In vitro experiments showed that the mutation alters agrin-dependent acetylcholine receptor aggregation, causes a constitutive activation of MuSK and a decrease in its agrin- and Dok-7-dependent phosphorylation...
- Synaptic dysfunction in congenital myasthenic syndromesDavid Beeson
Weatherall Institute of Molecular Medicine, The John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom
Ann N Y Acad Sci 1275:63-9. 2012..of the methods that can be used to define if a DNA sequence variant is pathogenic with reference to variants in DOK7. We highlight a new mechanism for disruption of AChR function, where a mutation in the AChR ɛ-subunit gene causes ..
- DOK7 congenital myasthenic syndromeJacqueline Palace
Clinical Neurology, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, United Kingdom
Ann N Y Acad Sci 1275:49-53. 2012Despite being a fairly recent discovery, DOK7 congenital myasthenic syndrome (CMS) is the third most common form of CMS in the United Kingdom. DOK7 is a postsynaptic protein associated with the AChR clustering pathway...
- Structure of the neuromuscular junction: function and cooperative mechanisms in the synapseMasaharu Takamori
Neurological Center, Kanazawa Nishi Hospital, Japan
Ann N Y Acad Sci 1274:14-23. 2012..and receptor tyrosine kinases; (2) postsynaptic acetylcholine receptor clustering mediated by the muscle-specific, Dok7-stimulated tyrosine kinase (MuSK) through two signaling mechanisms: one via agrin-Lrp4-MuSK (Ig1/2 domains) and the ..
- Salbutamol benefits children with congenital myasthenic syndrome due to DOK7 mutationsGeorgina Burke
Wessex Neurological Centre, Southampton General Hospital, Southampton, UK
Neuromuscul Disord 23:170-5. 2013Congenital myasthenic syndromes due to DOK7 mutations cause fatigable limb girdle weakness. Treatment with ephedrine improves muscle strength...
- [Congenital myasthenic syndromes]Kinji Ohno
Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine
Rinsho Shinkeigaku 52:1159-61. 2012..In the past two years, we diagnosed 15 cases with CMS in Japan, and identified mutations in 12 patients. All the mutations except for one are unique to Japanese patients. We assume that more CMS cases still remain undiagnosed in Japan...
- Pregnancy in congenital myasthenic syndromeL Servais
Service of therapeutic trials and databases, Institut de Myologie, Groupe Hospitalier Pitie Salpetriere, Paris, France
J Neurol 260:815-9. 2013..We report on 17 pregnancies in eight patients with CMS with mutations in CHRNA1, CHRNE, CHRND, GFPT1, COLQ, or DOK7. Symptoms worsened for six patients during at least one of their pregnancies, and one patient required ..
- DNA methylation profiling in breast cancer discordant identical twins identifies DOK7 as novel epigenetic biomarkerHolger Heyn
Cancer Epigenetics and Biology Program PEBC, Bellvitge Biomedical Research Institute IDIBELL, L Hospitalet, Barcelona, Catalonia 08907, Spain
Carcinogenesis 34:102-8. 2013..Confirming the results in an independent validation cohort of 21 twin pairs determined the docking protein DOK7 as a candidate for blood-based cancer diagnosis...
- DOK7 limb-girdle myasthenic syndrome mimicking congenital muscular dystrophyIbrahim Mahjneh
Department of Neurology, University of Oulu, Oulu, Finland
Neuromuscul Disord 23:36-42. 2013..3. As the DOK7 gene is located in this genetic interval, we considered it a potential candidate for this condition...
- The spectrum of mutations that underlie the neuromuscular junction synaptopathy in DOK7 congenital myasthenic syndromeJudith Cossins
Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK
Hum Mol Genet 21:3765-75. 2012..A subgroup of CMS patients have a recessively inherited limb-girdle pattern of weakness caused by mutations in DOK7. DOK7 encodes DOK7, an adaptor protein that is expressed in the skeletal muscle and heart and that is essential for ..
- [Congenital myasthenic syndromes: difficulties in the diagnosis, course and prognosis, and therapy--The French National Congenital Myasthenic Syndrome Network experience]B Eymard
Centre de référence des affections neuromusculaires Paris Est, Service de neurologie 2, Institut de Myologie, Hopital de la Pitie Salpetriere, 47 bd de l Hopital, 75013 Paris, France
Rev Neurol (Paris) 169:S45-55. 2013..prognosis of CMS was studied in a series of 79 patients recruited with the following gene mutations: CHRNA; CHRNE; DOK7; COLQ; RAPSN; AGRN; and MUSK...
- Congenital myasthenic syndrome: a brief reviewPaulo José Lorenzoni
Neuromuscular Disorders Unit, Division of Neurology, Department of Internal Medicine, Hospital de Clinicas da Universidade Federal do Parana, Curitiba, PR, Brazil
Pediatr Neurol 46:141-8. 2012..may be necessary to identify specific mutations in CHAT, COLQ, LAMB2, CHRNA, CHRNB, CHRND, CHRNE, CHRNG, RAPSN, DOK7, MUSK, AGRN, SCN4A, GFPT1, or PLEC1 genes...
- Activation of receptor protein-tyrosine kinases from the cytoplasmic compartmentYuji Yamanashi
Division of Genetics, Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Tokyo 108 8639, Japan
J Biochem 151:353-9. 2012..Given that failure of Dok-7 signaling causes myasthenia, and inhibition of cytohesin signaling reduces the proliferation of EGFR-dependent cancer cells, cytoplasmic activators of RTKs may provide new therapeutic targets...
- Current status of the congenital myasthenic syndromesAndrew G Engel
Department of Neurology, Mayo Clinic, Rochester, MN 55905, United States
Neuromuscul Disord 22:99-111. 2012..4, the muscle specific protein kinase (MuSK), agrin, downstream of tyrosine kinase 7 (Dok-7), and glutamine-fructose-6-phosphate transaminase 1 (GFPT1)...
- Structure and activation of MuSK, a receptor tyrosine kinase central to neuromuscular junction formationStevan R Hubbard
Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA Electronic address
Biochim Biophys Acta 1834:2166-9. 2013..In addition, Dok7, a cytoplasmic adaptor protein, is also required for MuSK activation in vivo...
- Congenital myasthenic syndrome with tubular aggregates caused by GFPT1 mutationsVelina Guergueltcheva
Department of Neurology, Friedrich Baur Institut, Ludwig Maximilians University, Munich, Germany
J Neurol 259:838-50. 2012..b>DOK7 mutations have been identified as causing the disorder in about half of the cases...
- Endosomal trafficking of the receptor tyrosine kinase MuSK proceeds via clathrin-dependent pathways, Arf6 and actinSusan Luiskandl
Center for Brain Research, Medical University of Vienna, Vienna, Austria
FEBS J 280:3281-97. 2013..MuSK activation by Dok7 mildly affects the localization of MuSK on the cell surface but has no effect on the rate of MuSK internalization...
- The role of MuSK in synapse formation and neuromuscular diseaseSteven J Burden
Molecular Neurobiology Program, Helen L and Martin S Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, NYU Medical School, New York, NY 10016, USA
Cold Spring Harb Perspect Biol 5:a009167. 2013..Mutations in MuSK and in genes that function in the MuSK signaling pathway, including Dok-7, cause congenital myasthenia, and autoantibodies to MuSK, Lrp4, and acetylcholine receptors are responsible for myasthenia gravis...
- Salbutamol therapy in congenital myasthenic syndrome due to DOK7 mutationPaulo J Lorenzoni
Neurology Division, Internal Medicine Department, Hospital de Clinicas, Universidade Federal do Parana, Curitiba, PR, Brazil
J Neurol Sci 331:155-7. 2013..In this study, we analyzed the effect of salbutamol in five patients with Dok-7 CMS...
- A mouse model of the slow channel myasthenic syndrome: Neuromuscular physiology and effects of ephedrine treatmentR G Webster
Neurosciences Group, Nuffield Dept of Clinical Neurosciences, University of Oxford, Oxford, UK
Exp Neurol 248:286-98. 2013..Ephedrine and salbutamol show clear benefit when used in the treatment of DOK7 or COLQ congenital myasthenic syndromes...
- DOK7 congenital myasthenic syndrome in childhood: early diagnostic clues in 23 childrenAndrea Klein
Department of Paediatric Neurology, University Children s Hospital, Zurich, Switzerland Dubowitz Neuromuscular Centre, Institute of Child Health and Great Ormond Street Hospital, London, UK Electronic address
Neuromuscul Disord 23:883-91. 2013Mutations in DOK7 are a common cause of congenital myasthenia. Treatment with ephedrine or salbutamol is effective, but diagnosis is often delayed...
- MuSK myasthenia gravis IgG4 disrupts the interaction of LRP4 with MuSK but both IgG4 and IgG1-3 can disperse preformed agrin-independent AChR clustersInga Koneczny
Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom
PLoS ONE 8:e80695. 2013..receptor-related protein-4 (LRP4), which then binds to MuSK; MuSK interaction with the intracellular protein Dok7 results in clustering of the acetylcholine receptors (AChRs) on the postsynaptic membrane...
- Dok-7 promotes slow muscle integrity as well as neuromuscular junction formation in a zebrafish model of congenital myasthenic syndromesJuliane S Muller
Institute of Human Genetics, International Centre for Life, Newcastle University, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK
Hum Mol Genet 19:1726-40. 2010..smaller than in the wild-type zebrafish, reminiscent of the neuromuscular endplate pathology seen in patients with DOK7 mutations...
- Structural factors influencing the efficacy of neuromuscular transmissionClarke R Slater
Institute of Neuroscience, Faculty of Medical Sciences, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE2 4HH, UK
Ann N Y Acad Sci 1132:1-12. 2008..This condition emphasizes the importance of structural features in achieving reliability of neuromuscular transmission...
- The roles of Dok family adapters in immunoreceptor signalingRyuichi Mashima
Division of Genetics, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Immunol Rev 232:273-85. 2009..Here, we review the physiological roles and underlying mechanisms of Dok family proteins...
- Ephedrine therapy in eight patients with congenital myasthenic syndrome due to DOK7 mutationsU Schara
Dept of Pediatric Neurology, University of Essen, Germany
Neuromuscul Disord 19:828-32. 2009In congenital myasthenic syndrome with DOK7 mutations ephedrine was reported to be beneficial in single patients. We carried out a small, open and prospective cohort study in eight European patients manifesting from birth to 12 years...
- Germline mutation in DOK7 associated with fetal akinesia deformation sequenceJ Vogt
Department of Medical and Molecular Genetics and WellChild Paediatric Research Centre, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK
J Med Genet 46:338-40. 2009....
- Dok-7 activates the muscle receptor kinase MuSK and shapes synapse formationAkane Inoue
Division of Genetics and Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Tokyo 108 8639, Japan
Sci Signal 2:ra7. 2009..These observations indicate that Dok-7 positively regulates neuromuscular synaptogenesis by controlling MuSK activity, its distribution, and its responsiveness to neural agrin...
- Dok-7/MuSK signaling and a congenital myasthenic syndromeY Yamanashi
Division of Genetics, Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Japan
Acta Myol 27:25-9. 2008..b>DOK7 has been found to be a major locus for mutations that underlie a genetic form of myasthenia with a characteristic '..
- A mammalian homolog of Drosophila tumorous imaginal discs, Tid1, mediates agrin signaling at the neuromuscular junctionJenny Linnoila
Molecular Pharmacology Graduate Training Program, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
Neuron 60:625-41. 2008..These results demonstrate that Tid1 is an essential component of the agrin signaling pathway, crucial for synaptic development...
- Congenital myasthenic syndromes in childhood: diagnostic and management challengesM Kinali
The Dubowitz Neuromuscular Centre, Great Ormond Street Hospital and Institute of Child Health, University College, London, UK
J Neuroimmunol 201:6-12. 2008..Mutations have been identified so far in 32/46 children: 10 RAPSN, 7 COLQ, 6 CHRNE, 7 DOK7, 1 CHRNA1 and 1 CHAT...
- Further observations in congenital myasthenic syndromesAndrew G Engel
Department of Neurology and Muscle Research Laboratory, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
Ann N Y Acad Sci 1132:104-13. 2008..4, MuSK, and Dok-7. Moreover, emerging genotype-phenotype correlations are providing clues for targeted mutation analysis. This review focuses on the recent observations in selected CMS...
- [Overview: MuSK/Dok-7]Masakatsu Motomura
The First Department of Internal Medicine, Graduate School of Biomedical Sciences, Nagasaki University
Nihon Rinsho 66:1140-8. 2008..Subsequently, mutations in Dok-7 as a cause of CMS were identified, providing evidence for a crucial role of Dok-7 in maintaining synaptic structure. Their effect on MuSK/Dok -7 function needs to be explored...
- Mutations causing DOK7 congenital myasthenia ablate functional motifs in Dok-7Johko Hamuro
Department of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo ku, Yushima, Tokyo 113 8510, Japan
J Biol Chem 283:5518-24. 2008..Both Dok-7 and MuSK are required for neuromuscular synaptogenesis. Mutations in DOK7 underlie a congenital myasthenic syndrome (CMS) associated with small and simplified neuromuscular synapses likely ..
- Downstream of tyrosine kinase/docking protein 6, as a novel substrate of tropomyosin-related kinase C receptor, is involved in neurotrophin 3-mediated neurite outgrowth in mouse cortex neuronsWei Qi Li
National Key Laboratory of Medical Molecular Biology, School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China
BMC Biol 8:86. 2010The downstream of tyrosine kinase/docking protein (Dok) adaptor protein family has seven members, Dok1 to Dok7, that act as substrates of multiple receptor tyrosine kinase and non-receptor tyrosine kinase...
- Mutations in MUSK causing congenital myasthenic syndrome impair MuSK-Dok-7 interactionRicardo A Maselli
Department of Neurology, School of Veterinary Medicine, University of California Davis, Davis, CA 95618, USA
Hum Mol Genet 19:2370-9. 2010....
- Ephedrine treatment in congenital myasthenic syndrome due to mutations in DOK7D Lashley
Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK
Neurology 74:1517-23. 2010..Patients usually do not respond to or worsen with the standard CMS treatments: cholinesterase inhibitors and 3,4-diaminopyridine. However, anecdotal reports suggest they may improve with ephedrine...
- Congenital myasthenic syndromes in 2012Andrew G Engel
Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
Curr Neurol Neurosci Rep 12:92-101. 2012..4, muscle-specific kinase, agrin, β2-laminin, downstream of tyrosine kinase 7, and glutamine-fructose-6-phosphate transaminase 1...
- Beneficial effects of albuterol in congenital endplate acetylcholinesterase deficiency and Dok-7 myastheniaTeerin Liewluck
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA
Muscle Nerve 44:789-94. 2011..EP AChE, Dok-7, and β(2)-laminin deficiencies respond favorably to ephedrine, but ephedrine can no longer be prescribed in the USA...
- [Genetic defects and disorders at the neuromuscular junction]Kinji Ohno
Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan
Brain Nerve 63:669-78. 2011..Acetylcholinesterase is inhibited by the nerve gas sarin and by organophosphate pesticides. This review focuses on the molecular bases underlying defects of AChR, rapsyn, Nav1.4, collagen Q, and choline acetyltransferase...
- [Molecular mechanisms underlying the formation of neuromuscular junction]Osamu Higuchi
Division of Genetics, Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Brain Nerve 63:649-55. 2011..Moreover, new evidence indicates that cyclin-dependent kinase 5 (Cdk5) regulates postsynaptic differentiation. In this review, we summarize the latest developments in molecular mechanisms underlying NMJ formation in vertebrates...
- The transcription factor Sp1 plays a crucial role in dok-7 gene expressionJohko Hamuro
Department of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, Tokyo 113 8510, Japan
Biochem Biophys Res Commun 408:293-9. 2011..Mutations of the human DOK7 gene underlie a limb-girdle type of congenital myasthenic syndrome, a group of disorders characterized by NMJ ..
- Investigation for RAPSN and DOK-7 mutations in a cohort of seronegative myasthenia gravis patientsEspen Homleid Alseth
Department of Clinical Medicine, University of Bergen, Bergen, Norway
Muscle Nerve 43:574-7. 2011..Because late-onset congenital myasthenic syndromes (CMSs) due to RAPSN or DOK7 mutations may be mistaken for SNMG, we investigated their frequency in a nationwide SNMG cohort.
- MuSK levels differ between adult skeletal muscles and influence postsynaptic plasticityAnna R Punga
Department of Neurobiology Pharmacology, Biozentrum, University of Basel, Basel, Switzerland
Eur J Neurosci 33:890-8. 2011..We believe that these findings are important for our understanding of adult muscle plasticity and the selective muscle involvement in neuromuscular disorders in which MuSK is diminished...
- Dok-7 regulates neuromuscular synapse formation by recruiting Crk and Crk-LPeter T Hallock
Molecular Neurobiology Program, Skirball Institute of Biomolecular Medicine, New York University Medical School, New York, New York 10016, USA
Genes Dev 24:2451-61. 2010....
- Motor endplate remodeling in some cases with congenital myasthenic syndromeAnna Fidzianska
Neuromuscular Unit, Medical Centre, Polish Academy of Science, Pawinskiego 5, 02 106 Warsaw, Poland
Folia Neuropathol 48:200-5. 2010..The conjunction of postsynaptic membrane paucity and its degeneration was a specific structural feature observed in the third syndrome with no established genetic defects...
- DOK7 mutations presenting as a proximal myopathy in French CanadiansMyriam Srour
Laboratoire de neurogénétique de la motricité, Centre de Recherche du CHUM, Montreal, Universite de Montreal, QC, Canada
Neuromuscul Disord 20:453-7. 2010b>DOK7 mutations cause a congenital myasthenic syndrome (OMIM 254300) characterized by a "limb-girdle" phenotype. We identified 7 French-Canadian patients with a previously undiagnosed proximal myopathy. A genome wide scan was performed...
- Congenital stridor with feeding difficulty as a presenting symptom of Dok7 congenital myasthenic syndromeChris G Jephson
Department of Otolaryngology, Great Ormond Street Hospital for Children and Institute of Child Health, Great Ormond Street, London, WC1N 3JH, UK
Int J Pediatr Otorhinolaryngol 74:991-4. 2010..from birth, but diagnosis is often delayed for several years, notably in post-synaptic CMS due to mutations in the DOK7 gene...
- RICARDO ANIBAL MASELLI; Fiscal Year: 2014..CHAT), rapsyn (RAPSN), the voltage-gated muscle sodium channel (SCN4A), the muscle-specific kinase (MUSK), Dok-7 (DOK7) and the fetal subunit of the AChR (CHRNG), have been demonstrated to be implicated in the pathogenesis of other ..
- SIGNALING BY MUSK, A COMPONENT OF THE AGRIN RECEPTORSTEVEN BURDEN; Fiscal Year: 2012..The experiments described here are designed to determine how Lrp4 and Dok-7, two newly discovered components of this signaling pathway mediate Agrin responsiveness, lead to MuSK phosphorylation and stimulate synaptic differentiation. ..
- STEVEN BURDEN; Fiscal Year: 2015..Moreover, mutations in genes that are downstream from Crk/Crk-L may likewise cause congenital myasthenia, so identifying the pathway downstream from Crk/Crk-L may reveal new genes responsible for congenital myasthenia. ..
- Role of DOK Proteins in Lung CancerMasaru Niki; Fiscal Year: 2012..In addition, we will extend these data to humans and attempt to identify human BASCs and determine if they express Dok proteins. ..
- Structure-Function Studies of the Receptor Tyrosine Kinase MuSKSTEVAN HUBBARD; Fiscal Year: 2009..By revealing the biochemical mechanisms underlying the formation of this important synapse, we will better understand, at a molecular level, how defects in this process give rise to neuromuscular disorders. ..
- STRUCTURAL STUDY OF THE INSULIN RECEPTOR TYROSINE KINASEStevan R Hubbard; Fiscal Year: 2010..By understanding at the molecular level how the insulin receptor is regulated, we hope to facilitate efforts to design small-molecule agonists and inhibitors that could potentially be used as anti-diabetic therapeutics. ..