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Genomes and Genes | David BeesonSummaryAffiliation: University of Oxford Country: UK Publications
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Publications
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...
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....- Structural abnormalities of the AChR caused by mutations underlying congenital myasthenic syndromesDavid Beeson
Neurosciences Group, Weatherall Institute of Molecular Medicine, The John Radcliffe, Headington, Oxford OX3 9DS, United Kingdom
Ann N Y Acad Sci 998:114-24. 2003..It was found that mutations within muscle AChRs are the most common cause of CMS. The majority are located within the epsilon-subunit gene and result in AChR deficiency... - 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. 2007..CMS due to DOK7 mutations are common within our UK cohort and is likely to be under-diagnosed; recognition of the phenotype will help clinical diagnosis, targeted genetic screening and appropriate management... - Diverse molecular mechanisms involved in AChR deficiency due to rapsyn mutationsJudy Cossins
Neurosciences Group, Weatherall Institute of Molecular Medicine, Churchill Hospital, Oxford, UK
Brain 129:2773-83. 2006..The disease severity of patients harbouring the compound allelic mutations was greater than that of patients with homozygous rapsyn mutation N88K, suggesting that the second mutant allele may largely determine severity... 
IgG1 antibodies to acetylcholine receptors in 'seronegative' myasthenia gravisMaria Isabel Leite
Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK
Brain 131:1940-52. 2008..These observations throw new light on different forms of MG paving the way for improved diagnosis and management, and the approaches used have applicability to other antibody-mediated conditions...- 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..The DOK7 gene is highly polymorphic, and within these many variants, we define a spectrum of mutations that can underlie DOK7 CMS that will inform in managing this disorder... - Non-radioactive serological diagnosis of myasthenia gravis and clinical features of patients from Tianjin, ChinaLi Yang
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, England, UK
J Neurol Sci 301:71-6. 2011..To establish non-radioactive assays for detection of antibodies (Abs) to the acetylcholine receptor (AChR) and to muscle specific kinase (MuSK). To show that the assays can be used in Tianjin for testing patients with MG... - Antibodies in myasthenia gravis and related disordersAngela Vincent
Neurosciences Group, Department of Clinical Neurology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom
Ann N Y Acad Sci 998:324-35. 2003..These antibodies are not found in AChR antibody-positive MG and are predominantly IgG4. MuSK antibody positivity appears to be associated with more severe bulbar disease that can be difficult to treat effectively... - Myasthenia gravis seronegative for acetylcholine receptor antibodiesAngela Vincent
Neurosciences Group, Weatherall Institute of Molecular Medicine and Department of Clinical Neurology, John Radcliffe Hospital, Oxford, United Kingdom
Ann N Y Acad Sci 1132:84-92. 2008..Overall, these results suggest that complement-activation may be an important pathogenic mechanism even in patients without conventional AChR antibodies... - Antibodies identified by cell-based assays in myasthenia gravis and associated diseasesAngela Vincent
Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, United Kingdom
Ann N Y Acad Sci 1274:92-8. 2012..The cell-based method is time consuming but has many advantages and may provide a gold standard for the future in the detection of pathogenic autoantibodies in patients with immune-mediated diseases... - Inhibition of acetylcholine receptor function by seronegative myasthenia gravis non-IgG factor correlates with desensitisationIan Spreadbury
Neurosciences Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom
J Neuroimmunol 162:149-56. 2005..The results suggest that, rather than acting indirectly as previously proposed, the SNMG factor may bind directly to an allosteric site that induces or enhances AChR desensitisation... - A novel congenital myasthenic syndrome due to decreased acetylcholine receptor ion-channel conductanceRichard Webster
Neurosciences Group, Weatherall Institute of Molecular Medicine, Headley Way, Oxford OX3 9DS, UK
Brain 135:1070-80. 2012..F266 deletion mutation revealed by the coinheritance of the low-expressor mutation p.εP282R... - Effect of sera from AChR-antibody negative myasthenia gravis patients on AChR and MuSK in cell culturesMaria Elena Farrugia
Neurosciences Group, Weatherall Institute of Molecular Medicine, Department of Clinical Neurology, University of Oxford, UK
J Neuroimmunol 185:136-44. 2007..Thus, although these results have, disappointingly, demonstrated little effect of MuSK antibodies on AChR expression, they do imply that SNMG antibodies act on AChR-associated pathways... - Lack of association between acetylcholine receptor epsilon polymorphisms and early-onset myasthenia gravisDomenico Marco Bonifati
Neurosciences Group, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom
Muscle Nerve 29:436-9. 2004..These data provide no evidence that heteroallelic mutations or polymorphisms in the AChR epsilon subunit are involved in the development of autoimmune early-onset MG but raise issues for future studies... - Spontaneous production of anti-IFN-alpha and anti-IL-12 autoantibodies by thymoma cells from myasthenia gravis patients suggests autoimmunization in the tumorHiroyuki Shiono
Neuroscience Group, Weatherall Institute for Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK
Int Immunol 15:903-13. 2003..With these molecules, it should be easier to identify provoking cell type(s) that may give novel additional clues to autoimmunization against T-cell epitopes from the more complex AChR... - The search for new antigenic targets in myasthenia gravisJudith Cossins
Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom
Ann N Y Acad Sci 1275:123-8. 2012..These assays, combined with use of myotube cultures to explore the effects of the antibodies, enable us to begin to identify new antigenic targets and test antibody pathogenicity in vitro... - Identification of DPAGT1 as a new gene in which mutations cause a congenital myasthenic syndromeKatsiaryna Belaya
Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom
Ann N Y Acad Sci 1275:29-35. 2012..This finding demonstrates that impairment of the N-linked glycosylation pathway can lead to the development of CMS... - Congenital myasthenic syndromes due to mutations in ALG2 and ALG14Judith Cossins
Neurosciences Group, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK
Brain 136:944-56. 2013..Our findings suggest that treatment with cholinesterase inhibitors may improve muscle function in many of the congenital disorders of glycosylation... - Preferential expression of AChR epsilon-subunit in thymomas from patients with myasthenia gravisCalman A MacLennan
Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK
J Neuroimmunol 201:28-32. 2008..The greater abundance of mRNA for AChR epsilon-subunit than for other subunits suggests that the AChR epsilon-subunit may play a distinctive role in autosensitization in MG-associated thymomas, particularly those of type A or AB... - Myasthenia gravis in a woman with congenital AChR deficiency due to epsilon-subunit mutationsRebecca Croxen
Neurosciences Group, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford, United Kingdom
Neurology 58:1563-5. 2002..The younger sister developed MG at 34 years. This unusual case raises the possibility that genetic defects of the AChR might be a factor in the etiology of autoimmune MG... - Mutations in congenital myasthenic syndromes reveal an epsilon subunit C-terminal cysteine, C470, crucial for maturation and surface expression of adult AChRJohn Ealing
Neurosciences Group, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK
Hum Mol Genet 11:3087-96. 2002.... - Hairpin DNAzymes: a new tool for efficient cellular gene silencingAmr Abdelgany
Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe Hospital, Oxford OX3 9DS, UK
J Gene Med 9:727-38. 2007..Chemical modifications can be introduced into the binding arms to increase stability but these may alter catalytic activity and in some cases increase cell toxicity... - Detection and characterization of MuSK antibodies in seronegative myasthenia gravisJohn McConville
Weatherall Institute of Molecular Medicine and Department of Clinical Neurology, Oxford, UK
Ann Neurol 55:580-4. 2004..They bind to the extracellular Ig-like domains of soluble or native MuSK. Surprisingly they are predominantly in the IgG4 subclass. MuSK-antibody associated MG may be different in etiological and pathological mechanisms... - Allele-specific silencing of a pathogenic mutant acetylcholine receptor subunit by RNA interferenceAmr Abdelgany
Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, UK
Hum Mol Genet 12:2637-44. 2003.... - 126th International Workshop: congenital myasthenic syndromes, 24-26 September 2004, Naarden, the NetherlandsDavid Beeson
Neurosciences Group, Weatherall Institute of Molecular Medicine, The John Radcliff, Oxford, UK
Neuromuscul Disord 15:498-512. 2005 - A mouse model of AChR deficiency syndrome with a phenotype reflecting the human conditionJudy Cossins
Neuroscience Group, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford, UK
Hum Mol Genet 13:2947-57. 2004.... - Mutations in DPAGT1 cause a limb-girdle congenital myasthenic syndrome with tubular aggregatesKatsiaryna Belaya
Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, UK
Am J Hum Genet 91:193-201. 2012.... - Clinical features in a series of fast channel congenital myasthenia syndromeJacqueline Palace
Department of Neurology, John Radcliffe Hospital, Oxford, UK
Neuromuscul Disord 22:112-7. 2012..Referral to a specialist paediatric respiratory centre and regular resuscitation training for parents are recommended... - Muscle dysfunction caused by a KATP channel mutation in neonatal diabetes is neuronal in originRebecca H Clark
Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford, OX1 3PT, UK
Science 329:458-61. 2010..These findings suggest that drugs targeted against neuronal, rather than muscle, KATP channels are needed to treat the motor deficits and that such drugs require high blood-brain barrier permeability... - Slow channel congenital myasthenic syndrome responsive to a combination of fluoxetine and salbutamolSarah Finlayson
Neuroscience Group, Weatherall Institute of Molecular Medicine, The John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK
Muscle Nerve 47:279-82. 2013..Slow channel congenital myasthenic syndrome is a dominant disorder characterized by prolonged acetylcholine receptor ion-channel activation... - The agrin/muscle-specific kinase pathway: new targets for autoimmune and genetic disorders at the neuromuscular junctionYohan Liyanage
Neurosciences Group, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK
Muscle Nerve 25:4-16. 2002..We then review the development of the NMJ, focusing on the important roles of nerve-derived agrin and MuSK in clustering of AChRs and other essential components of the NMJ... - Aquaporin-4 antibodies in neuromyelitis optica and longitudinally extensive transverse myelitisPatrick Waters
Neurosciences Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, England
Arch Neurol 65:913-9. 2008..There is increasing recognition of antibody-mediated immunotherapy-responsive neurologic diseases and a need for appropriate immunoassays... - 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..The study of these disorders is proving highly informative for understanding the diverse molecular mechanisms that can underlie synaptic dysfunction... - N-methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexesSarosh R Irani
Department of Clinical Neurology, L6 West Wing, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK
Brain 133:1655-67. 2010..Four patients, who only had temporal lobe epilepsy without oligoclonal bands, may represent restriction to the first stage... - Antibodies to acetylcholine receptor in parous women with myasthenia: evidence for immunization by fetal antigenIan Matthews
Neurosciences Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom
Lab Invest 82:1407-17. 2002.... - Ribozymes and siRNA for the treatment of diseases of the nervous systemMatthew J Wood
Department of Human Anatomy and Genetics, Oxford University, South Parks Road, Oxford, OX1 3QX, UK
Curr Opin Mol Ther 5:383-8. 2003..This review will assess the potential of these RNA-based therapeutic strategies and the challenges ahead in their application to the treatment of neurological disease... - The congenital myasthenic syndromesJackie Palace
Department of Clinical Neurology, Level 3, West Wing, John Radcliffe Hospital, Headley Way, Headington OX3 9DU, UK
J Neuroimmunol 201:2-5. 2008..Although each syndrome results from defective synaptic transmission at the neuromuscular junction, the patients show a variable set of phenotypes. Here, we provide a brief clinical review... - Therapeutic gene silencing in the nervous systemMatthew J A Wood
Department of Human Anatomy and Genetics, Oxford University, Oxford, UK
Hum Mol Genet 12:R279-84. 2003.... - Mutation analysis of CHRNA1, CHRNB1, CHRND, and RAPSN genes in multiple pterygium syndrome/fetal akinesia patientsJulie Vogt
Department of Medical and Molecular Genetics and WellChild Paediatric Research Centre, Division of Reproductive and Child Health, University of Birmingham, Birmingham B15 2TT, UK
Am J Hum Genet 82:222-7. 2008..Functional studies were consistent with the hypothesis that whereas incomplete loss of rapsyn function may cause congenital myasthenia, more severe loss of function can result in a lethal fetal akinesia phenotype... - 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.... - 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..Ablation or disruption of these functional elements in Dok-7 probably underlies the neuromuscular junction synaptopathy observed in DOK7 CMS... - An IRF8-binding promoter variant and AIRE control CHRNA1 promiscuous expression in thymusMatthieu Giraud
INSERM, U580, 75015 Paris, France
Nature 448:934-7. 2007.... - CHRND mutation causes a congenital myasthenic syndrome by impairing co-clustering of the acetylcholine receptor with rapsynJuliane S Muller
Department of Neurology, Friedrich Baur Institute, Ludwig Maximilians University, Munich, Germany
Brain 129:2784-93. 2006..Introduction of the same mutation in the epsilon subunit had no effect on AChR clustering indicating a special role of the delta subunit in AChR-rapsyn interactions... - Rhabdomyosarcoma lysis by T cells expressing a human autoantibody-based chimeric receptor targeting the fetal acetylcholine receptorStefan Gattenlohner
Institute of Pathology, University of Wuerzburg, Wuerzburg, Germany
Cancer Res 66:24-8. 2006.... - Isolation of potent human Fab fragments against a novel highly immunogenic region on human muscle acetylcholine receptor which protect the receptor from myasthenic autoantibodiesEfrosini Fostieri
Department of Biochemistry, Hellenic Pasteur Institute, Athens, Greece
Eur J Immunol 35:632-43. 2005..Furthermore, this Fab protected surface AChR in cell cultures against MG autoantibody-induced antigenic modulation, suggesting a potential therapeutic use in MG, especially in combination with a human anti-MIR Fab... - Mutation history of the roma/gypsiesBharti Morar
Laboratory of Molecular Genetics, Western Australian Institute for Medical Research and UWA Centre for Medical Research, University of Western Australia, Perth, Australia
Am J Hum Genet 75:596-609. 2004....