Research Topics
Genomes and GenesSpecies | ANDREW GEORGE ENGELSummaryAffiliation: Mayo Clinic Country: USA Publications
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Publications
Gene symbol: CHRNE. Disease: Endplate acetylcholine receptor deficiencyK Ohno
Department of Neurogenetics and Bioinformatics, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550, Japan
Hum Genet 117:301. 2005
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...- New horizons for congenital myasthenic syndromesAndrew G Engel
Neuromuscular Research Laboratory, Department of Neurology, Mayo Clinic, Rochester, Minnesota Receptor Biology Laboratory, Department of Physiology and Biomedical Engineering, and Department of Neurology, Mayo Clinic, Rochester, Minnesota
Ann N Y Acad Sci 1275:54-62. 2012.... - 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..Despite these advances, the molecular basis of some phenotypically characterized CMS remains elusive. Moreover, other types of CMS and disease genes likely exist and await discovery... - Congenital myasthenic syndromes: progress over the past decadeAndrew G Engel
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, Minnesota 55905, USA
Muscle Nerve 27:4-25. 2003..In a subset of CMS patients, endplate AChR deficiency is caused by mutations in rapsyn, a molecule that plays a critical role in concentrating AChR in the postsynaptic membrane... - Congenital myasthenic syndromes: A diverse array of molecular targetsAndrew G Engel
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905
J Neurocytol 32:1017-37. 2003.... - Current understanding of congenital myasthenic syndromesAndrew G Engel
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, Minnesota 55905, USA
Curr Opin Pharmacol 5:308-21. 2005..Recent crystallography studies of choline acetyltransferase and homology structural models of the acetylcholine receptor are providing further clues to how point mutations alter protein function... - Sleuthing molecular targets for neurological diseases at the neuromuscular junctionAndrew G Engel
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, Minnesota 55905, USA
Nat Rev Neurosci 4:339-52. 2003 - Light on limb-girdle myastheniaAndrew G Engel
Department of Neurology, Mayo Clinic Rochester, MN, USA
Brain 129:1938-9. 2006 - Congenital myasthenic syndromes: multiple molecular targets at the neuromuscular junctionAndrew G Engel
Neuromuscular Disease Research Laboratory, Department of Neurology, Mayo Clinic, Rochester, Minnesota 55905, USA
Ann N Y Acad Sci 998:138-60. 2003..In a subset of CMS patients, endplate AChR deficiency is caused by mutations in rapsyn, a molecule that plays a critical role in concentrating AChR in the postsynaptic membrane... - The spectrum of congenital myasthenic syndromesAndrew G Engel
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA
Mol Neurobiol 26:347-67. 2002..Future studies will likely uncover new types of CMS that reside in molecules governing quantal release, organization of the synaptic basal lamina, and expression and aggregation of AChR on the postsynaptic junctional folds... - The therapy of congenital myasthenic syndromesAndrew G Engel
Department of Neurology, Mayo Clinic, Rochester, Minnesota 55905, USA
Neurotherapeutics 4:252-7. 2007..Ephedrine has beneficial effects in some CMSs but its mechanism of action is not understood... - 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... - What have we learned from the congenital myasthenic syndromesAndrew G Engel
Department of Neurology and Muscle Research Laboratory, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
J Mol Neurosci 40:143-53. 2010..Mutations in EP-specific proteins also prompted expression studies that proved pathogenicity, highlighted important functional domains of the abnormal proteins, and pointed to rational therapy... 
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....- Rapsyn mutations in humans cause endplate acetylcholine-receptor deficiency and myasthenic syndromeKinji Ohno
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA
Am J Hum Genet 70:875-85. 2002..Expression studies in HEK cells indicate that none of the mutations hinders rapsyn self-association but that all three diminish coclustering of AChR with rapsyn... - Subunit-specific contribution to agonist binding and channel gating revealed by inherited mutation in muscle acetylcholine receptor M3-M4 linkerXin-ming Shen
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA
Brain 128:345-55. 2005..The overall studies reveal subunit asymmetry in the contributions of the M3-M4 loops in optimizing AChR activation through allosteric links to the channel and the agonist binding site... - Mutation causing severe myasthenia reveals functional asymmetry of AChR signature cystine loops in agonist binding and gatingXin Ming Shen
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, Minnesota 55905, USA
J Clin Invest 111:497-505. 2003..The overall findings reveal functional asymmetry between cys-loops of the different AChR subunits in contributing to ACh binding and channel gating... - Congenital myasthenia-related AChR delta subunit mutation interferes with intersubunit communication essential for channel gatingXin Ming Shen
Muscle Research Laboratory, Department of Neurology, Receptor Biology Laboratory, Mayo Clinic, Rochester, Minnesota 55905, USA
J Clin Invest 118:1867-76. 2008..Thus, deltaL42 is part of an intersubunit network that enables ACh binding to rapidly open the AChR channel, which may be compromised in patients with CM... - Familial cardioneuromyopathy with hyaline masses and nemaline rods: a novel phenotypeDuygu Selcen
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA
Ann Neurol 51:224-34. 2002.... - Correlation of muscle biopsy, clinical course, and outcome in PM and sporadic IBMNizar Chahin
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
Neurology 70:418-24. 2008..To correlate muscle biopsy findings with prebiopsy and postbiopsy clinical course and response to therapy in polymyositis (PM) and sporadic inclusion body myositis (IBM)... - Slow-channel mutation in acetylcholine receptor alphaM4 domain and its efficient knockdownXin-ming Shen
Neuromuscular Research Laboratory and Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
Ann Neurol 60:128-36. 2006..Efficient and selective knockdown of the mutant allele holds promise of therapeutic gene silencing... - Myasthenic syndrome caused by mutation of the SCN4A sodium channelAkira Tsujino
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA
Proc Natl Acad Sci U S A 100:7377-82. 2003..The V1442E mutation in SCN4A defines a novel disease mechanism and a novel phenotype with myasthenic features... - Naturally occurring mutations at the acetylcholine receptor binding site independently alter ACh binding and channel gatingSteven M Sine
Receptor Biology Laboratory, Department of Physiology and Biophysics, and Mayo Foundation, Rochester, MN 55905, USA
J Gen Physiol 120:483-96. 2002..The overall results show that key residues at the ACh binding site differentially stabilize the agonist bound to closed, open and desensitized states, and provide a set point for gating of the channel... - Recent advances in Cys-loop receptor structure and functionSteven M Sine
Department of Physiology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
Nature 440:448-55. 2006..Namely, analyses of disease-causing mutations have clarified receptor structure-function relationships as well as mechanisms governing the postsynaptic response... - Recent structural and mechanistic insights into endplate acetylcholine receptorsSteven M Sine
Receptor Biology Laboratory, Departments of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
Ann N Y Acad Sci 1132:53-60. 2008..Structural models of the human AChR enable precise mapping of disease-causing mutations, while studies of the speed with which single AChR channels open and close cast light on pathogenic mechanisms... - Treatment of slow-channel congenital myasthenic syndrome with fluoxetineC Michel Harper
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
Neurology 60:1710-3. 2003..Both patients showed marked subjective and objective improvement by quantitative muscle strength testing and electromyography... - Mutations in ZASP define a novel form of muscular dystrophy in humansDuygu Selcen
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA
Ann Neurol 57:269-76. 2005.... - Mechanistic diversity underlying fast channel congenital myasthenic syndromesSteven M Sine
Receptor Biology Laboratory, Department of Physiology and Biophysics, Mayo Medical School, Rochester, Minnesota 55905, USA
Ann N Y Acad Sci 998:128-37. 2003..This review focuses on new mechanisms underlying the FCCMS... - Mutation in BAG3 causes severe dominant childhood muscular dystrophyDuygu Selcen
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, NY, USA
Ann Neurol 65:83-9. 2009..Bag3, another Z-disk-associated protein, has antiapoptotic properties, and its targeted deletion in mice causes fulminant myopathy with early lethality. We therefore searched for mutations in BAG3 in 53 unrelated MFM patients... - A frameshifting mutation in CHRNE unmasks skipping of the preceding exonKinji Ohno
Department of Neurology, Mayo Clinic, Rochester, MN, USA
Hum Mol Genet 12:3055-66. 2003..Indeed, we found that epsilonEF157V and epsilonE154X in exon 6, observed in two other patients, caused aberrant splicing of exon 6... - Myofibrillar myopathy caused by novel dominant negative alpha B-crystallin mutationsDuygu Selcen
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA
Ann Neurol 54:804-10. 2003.... - Congenital myasthenic syndromes: genetic defects of the neuromuscular junctionKinji Ohno
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
Curr Neurol Neurosci Rep 2:78-88. 2002..Null mutations in both alleles of other AChR subunits are likely lethal, owing to absence of a substituting subunit... - Myofibrillar myopathy: clinical, morphological and genetic studies in 63 patientsDuygu Selcen
Department of Neurology, Neuromuscular Research Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
Brain 127:439-51. 2004..Further advances in defining the molecular causes of MFM will probably come from linkage studies of informative kinships or from systematic search for mutations in proteins participating in the intricate network supporting the Z-disk... - E-box mutations in the RAPSN promoter region in eight cases with congenital myasthenic syndromeKinji Ohno
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA
Hum Mol Genet 12:739-48. 2003..Impaired transcriptional activities of the RAPSN promoter region predict reduced rapsyn expression and endplate acetylcholine receptor deficiency... - Sporadic centronuclear myopathy with muscle pseudohypertrophy, neutropenia, and necklace fibers due to a DNM2 mutationTeerin Liewluck
Department of Neurology and Muscle Research Laboratory, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
Neuromuscul Disord 20:801-4. 2010..1269C>T (p.Arg369Trp) mutation. Necklace fibers were considered as a pathological hallmark of late onset X-linked CNM due to mutations in MTM1 but have not been observed in DNM2-CNM. The findings broaden the features of DNM2-myopathy... - Mutations in myotilin cause myofibrillar myopathyDuygu Selcen
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA
Neurology 62:1363-71. 2004..The authors' objective was to determine whether mutations in myotilin, a key Z-disk component and the disease protein in limb-girdle muscular dystrophy (LGMD) 1A, are another cause of MFM... - Are MuSK antibodies the primary cause of myasthenic symptoms?Duygu Selcen
Department of Neurology and Neuromuscular Disease Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA
Neurology 62:1945-50. 2004..To investigate the morphologic, electrophysiologic, and molecular correlates of muscle-specific tyrosine kinase-seropositive [MuSK(+)] myasthenia gravis (MG)... - Sporadic late onset nemaline myopathyNizar Chahin
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
Neurology 65:1158-64. 2005..2) The diagnosis is confirmed by visualizing the rods in trichrome or immunostained cryosections. 3) An associated monoclonal gammopathy heralds an unfavorable prognosis... - Congenital myasthenic syndromesAndrew G Engel
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, Minnesota 55905, USA
Adv Neurol 88:203-15. 2002 - Myasthenic syndrome caused by plectinopathyD Selcen
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
Neurology 76:327-36. 2011..Defects in plectin cause epidermolysis bullosa simplex (EBS), muscular dystrophy (MD), and sometimes pyloric atresia. Association of EBS with a myasthenic syndrome (MyS) was documented in a single patient in 1999... - Congenital myasthenic syndromesKinji Ohno
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
Eur J Paediatr Neurol 7:227-8. 2003 - Commonality of TRIM32 mutation in causing sarcotubular myopathy and LGMD2HBenedikt G H Schoser
Department of Neurology, Friedrich Baur Institute, Ludwig Maximilians University, Munich, Germany
Ann Neurol 57:591-5. 2005..The TRIM32 mutation found in the STM patients is identical to the causative mutation for LGMD2H (D487N), Haplotype analysis shows that the disease chromosomes share common ancestry... - Pathogenic point mutations in a transmembrane domain of the epsilon subunit increase the Ca2+ permeability of the human endplate ACh receptorAmalia Di Castro
Istituto Pasteur Fondazione Cenci Bolognetti and Dipartimento di Fisiologia Umana e Farmacologia, Università La Sapienza P le A Moro 5 I 00185 Roma, Italy
J Physiol 579:671-7. 2007.... - 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 - Structural abnormalities at neuromuscular synapses lacking multiple syntrophin isoformsMarvin E Adams
Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195, USA
J Neurosci 24:10302-9. 2004..We conclude that both alpha-syntrophin and beta2-syntrophin play distinct roles in forming and maintaining NMJ structure and that each syntrophin can partially compensate for the loss of the other... - Gene symbol: CHRNE. Disease: Endplate acetylcholine receptor deficiencyK Ohno
Department of Neurogenetics and Bioinformatics, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550, Japan
Hum Genet 117:295. 2005 - Gene symbol: CHRNE. Disease: Endplate acetylcholine receptor deficiencyK Ohno
Department of Neurogenetics and Bioinformatics, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550, Japan
Hum Genet 117:301. 2005 - Gene symbol: CHRNE. Disease: Endplate acetylcholine receptor deficiencyK Ohno
Department of Neurogenetics and Bioinformatics, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550, Japan
Hum Genet 117:302. 2005 - IBM-type inclusions in a patient with slow-channel syndrome caused by a mutation in the AChR epsilon subunitAnna Fidzianska
Neuromuscular Unit, Medical Research Centre, Pol Ac Sci Pawinskiego 5, 02 106 Warsaw, Poland
Neuromuscul Disord 15:753-9. 2005..Molecular genetic studies revealed a novel valine to phenylalanine mutation (epsilonV259F) in the M2 domain of the acetylcholine receptor. Coexistence of the slow-channel syndrome with a feature of IBM has not been observed before... - The human adult subtype ACh receptor channel has high Ca2+ permeability and predisposes to endplate Ca2+ overloadingSergio Fucile
Pasteur Institute Cenci Bolognetti Foundation and Department of Human Physiology and Pharmacology and Centre of Excellence for Biology and Molecular Medicine, University of Rome La Sapienza, Piazzale Aldo Moro 5 I 00185 Rome, Italy
J Physiol 573:35-43. 2006..However, the intrinsically high Ca2+ permeability of human AChRs probably predisposes to development of the endplate myopathy when opening events of the AChR channel are prolonged by altered AChR-channel kinetics... - Splicing abnormalities in congenital myasthenic syndromesKinji Ohno
Division of Neurogenetics and Bioinformatics, Department of Advanced Medical Science, Nagoya University Graduate School of Medicine, Japan
Acta Myol 24:50-4. 2005..Splicing mutations may be more frequent than suspected, and one must always be aware of possible splicing abnormalities when analyzing human mutations... - C-terminal and heparin-binding domains of collagenic tail subunit are both essential for anchoring acetylcholinesterase at the synapseLewis M Kimbell
Department of Cell Biology and Anatomy and Neuroscience Program, University of Miami School of Medicine, Miami, Florida 33136, USA
J Biol Chem 279:10997-1005. 2004..Our studies establish that the CTD mutations indeed compromise anchoring of ColQ and that both HSBD and CTD are essential for anchoring ColQ to the synaptic basal lamina... - Novel truncating RAPSN mutations causing congenital myasthenic syndrome responsive to 3,4-diaminopyridineBrenda L Banwell
Department of Pediatrics Neurology, The Hospital for Sick Children, University of Toronto, Canada
Neuromuscul Disord 14:202-7. 2004.... - Congenital myasthenic syndromes: gene mutationsKinjii Ohno
Neuromuscul Disord 14:117-22. 2004 - Congenital myasthenic syndromes:gene mutationsKinji Ohno
Neuromuscul Disord 13:854-7. 2003 - Choline acetyltransferase structure reveals distribution of mutations that cause motor disordersYiying Cai
Department of Molecular and Cellular Biochemistry, and Center for Structural Biology, University of Kentucky, Lexington, KY 40536, USA
EMBO J 23:2047-58. 2004..The structure indicates how ChAT is regulated by phosphorylation and reveals an unusual pattern of basic surface patches that may mediate membrane association or macromolecular interactions... - Effects of ginsenosides, active components of ginseng, on nicotinic acetylcholine receptors expressed in Xenopus oocytesSeok Choi
National Research Laboratory for the Study of Ginseng Signal Transduction and Department of Physiology, College of Veterinary Medicine, Chonnam National University, Kwangju, South Korea
Eur J Pharmacol 442:37-45. 2002..These results indicate that ginsenosides might regulate nicotinic acetylcholine receptors in a differential manner and this regulation might be one of the pharmacological actions of Panax ginseng... - Reconstitution of paired T cell receptor alpha- and beta-chains from microdissected single cells of human inflammatory tissuesSabine Seitz
Institute for Clinical Neuroimmunology, Ludwig Maximilians University, D-81377 Munich, Germany
Proc Natl Acad Sci U S A 103:12057-62. 2006..After functional reconstitution of the alphabeta-pairs, their antigen-recognition properties could be studied. Our results open avenues for combined analysis of the full TCR alpha- and beta-chain repertoire in human inflammatory tissues... - Translating research into treatmentsJohn H Noseworthy
Neurology 71:232-3. 2008
Research Grants
- CONGENITAL MYASTHENIC SYNDROMESAndrew Engel; Fiscal Year: 2001..Moreover, recognition of spontaneous mutations in the EP nicotinic AChR should spur the search for mutations in neuronal nicotinic AChRs and other ligand-gated channels in various neurologic and psychiatric disorders. ..
- CONGENITAL MYASTHENIC SYNDROMESAndrew Engel; Fiscal Year: 2006..abstract_text> ..
- CONGENITAL MYASTHENIC SYNDROMESAndrew Engel; Fiscal Year: 2007..They frequently go undiagnosed or misdiagnosed yet their consequences are often highly disabling. The CMS will be studied by a multifaceted approach that will improve their diagnosis, treatment, and prevention. ..
- ELECTRON MICROSCOPY OF MYOPATHIESAndrew Engel; Fiscal Year: 1980..In carnitine deficiency cultured muscle cells will be studied for a postulated abnormality of carnitine transport. The biochemical basis of an adult onset polyglucosan storage disease will be investigated...
- ELECTRON MICROSCOPY OF MYOPATHIESAndrew Engel; Fiscal Year: 1990..In dermatomyositis the hypothesis will be tested that the pathologic features of the disease are mediated by a circulating autoantibody...
- ELECTRON MICROSCOPY OF MYOPATHIESAndrew Engel; Fiscal Year: 1993..In the newly discovered mitochondrial encephalomyopathy due to coenzyme Q10 deficiency, the hypothesis will be tested that the disorder is caused by a defect in the mitochondrial biosynthesis of coenzyme Q10...
- CONGENITAL MYASTHENIC SYNDROMESANDREW GEORGE ENGEL; Fiscal Year: 2010..They frequently go undiagnosed or misdiagnosed yet their consequences are often highly disabling. The CMS will be studied by a multifaceted approach that will improve their diagnosis, treatment, and prevention. ..