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Genomes and Genes | K OhnoSummaryAffiliation: Mayo Clinic Country: USA Publications
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Publications
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...- 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... - 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... - Lack of founder haplotype for the rapsyn N88K mutation: N88K is an ancient founder mutation or arises from multiple foundersK Ohno
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA
J Med Genet 41:e8. 2004 - 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... - 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... - Congenital myasthenic syndrome caused by low-expressor fast-channel AChR delta subunit mutationX M Shen
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA
Neurology 59:1881-8. 2002..To determine the molecular basis of a disabling congenital myasthenic syndrome (CMS) observed in two related and one unrelated Arab kinship... - Mutation causing congenital myasthenia reveals acetylcholine receptor beta/delta subunit interaction essential for assemblyP A Quiram
Receptor Biology Laboratory, Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota 55905, USA
J Clin Invest 104:1403-10. 1999..The findings imply that the mutated residues are positioned at the interface between beta and delta subunits and demonstrate contribution of this local region of the long cytoplasmic loop to AChR assembly... - Congenital myasthenic syndromes due to heteroallelic nonsense/missense mutations in the acetylcholine receptor epsilon subunit gene: identification and functional characterization of six new mutationsK Ohno
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic and Foundation, Rochester, MN 55905, USA
Hum Mol Genet 6:753-66. 1997..The consequences of the endplate AChR deficiency are mitigated by persistent expression of gamma-AChR, changes in the release of transmitter quanta and appearance of multiple endplate regions on the muscle fiber... - New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndromeA G Engel
Department of Neurology, Mayo Clinic and Foundation, Rochester, MN 55905, USA
Hum Mol Genet 5:1217-27. 1996..The safety margin of neuromuscular transmission is compromised by AChR loss from the junctional folds and by a depolarization block owing to temporal summation of prolonged end plate potentials at physiologic rates of stimulation... - Fundamental gating mechanism of nicotinic receptor channel revealed by mutation causing a congenital myasthenic syndromeH L Wang
Receptor Biology Laboratory, Department of Physiology and Biophysics, Mayo Foundation, Rochester, Minnesota 55905, USA
J Gen Physiol 116:449-62. 2000..The findings further suggest that the fundamental gating mechanism of the AChR channel can be explained by a corrugated energy landscape superimposed on a steeply sloped energy well... - Acetylcholine receptor M3 domain: stereochemical and volume contributions to channel gatingH L Wang
Department of Physiology and Biophysics, Mayo Foundation, Rochester, Minnesota 55905, USA
Nat Neurosci 2:226-33. 1999..Thus, we demonstrate a functional role for the M3 domain as a key component of the nicotinic acetylcholine receptor channel-gating mechanism... - Congenital end-plate acetylcholinesterase deficiency caused by a nonsense mutation and an A-->G splice-donor-site mutation at position +3 of the collagenlike-tail-subunit gene (COLQ): how does G at position +3 result in aberrant splicing?K Ohno
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
Am J Hum Genet 65:635-44. 1999..We conclude that, with G at +3, normal splicing generally depends on the concordance that residues at +4 to +6 have with U1 snRNA, but other cis-acting elements may also be important in assuring the fidelity of splicing... - Spectrum of splicing errors caused by CHRNE mutations affecting introns and intron/exon boundariesK Ohno
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA
J Med Genet 42:e53. 2005..Only three of the eight intronic splice site mutations of CHRNE reported to date have had their splicing consequences characterised... - Slow-channel myasthenic syndrome caused by enhanced activation, desensitization, and agonist binding affinity attributable to mutation in the M2 domain of the acetylcholine receptor alpha subunitM Milone
Muscle Research Laboratory, Department of Neurology, Mayo Foundation, Rochester, Minnesota 55905, USA
J Neurosci 17:5651-65. 1997.... - The spectrum of mutations causing end-plate acetylcholinesterase deficiencyK Ohno
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
Ann Neurol 47:162-70. 2000.... - Myasthenic syndrome due to defects in rapsyn: Clinical and molecular findings in 39 patientsM Milone
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
Neurology 73:228-35. 2009..Pathogenic mutations in rapsyn result in endplate acetylcholine receptor (AChR) deficiency and are a common cause of postsynaptic congenital myasthenic syndromes... - End-plate acetylcholine receptor deficiency due to nonsense mutations in the epsilon subunitA G Engel
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
Ann Neurol 40:810-7. 1996..No channel activity could be recorded from HEK cells expressing epsilon 1293insG-AChR. Expression of gamma-AChR at the EPs may serve as the means of phenotypic rescue from potentially fatal nonsense mutations in the epsilon-subunit gene... - Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor epsilon subunitK Ohno
Muscle Research Laboratory, Department of Neurology, Mayo Foundation, Rochester, Minnesota 55905, USA
Neuron 17:157-70. 1996..Studies of the engineered epsilon P121L AChR revealed a markedly decreased rate of channel opening, little change in affinity of the resting state for ACh, but reduced affinity of the open channel and desensitized states... - Mutation of the acetylcholine receptor alpha subunit causes a slow-channel myasthenic syndrome by enhancing agonist binding affinityS M Sine
Department of Physiology and Biophysics, Mayo Foundation, Rochester, Minnesota 55905, USA
Neuron 15:229-39. 1995..Thus, ACh binding affinity can dictate the time course of the synaptic response, and alpha G153 contributes to the low binding affinity for ACh needed to speed the decay of the synaptic response... - Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humansK Ohno
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA
Proc Natl Acad Sci U S A 98:2017-22. 2001.... - 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... - Human endplate acetylcholinesterase deficiency caused by mutations in the collagen-like tail subunit (ColQ) of the asymmetric enzymeK Ohno
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA
Proc Natl Acad Sci U S A 95:9654-9. 1998.... - 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... - 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 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.... - 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... - 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... - 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... - 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... - 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... - 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... - 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 - 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 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... - Congenital myasthenic syndrome caused by prolonged acetylcholine receptor channel openings due to a mutation in the M2 domain of the epsilon subunitK Ohno
Department of Neurology, Mayo Clinic and Foundation, Rochester, MN 55905
Proc Natl Acad Sci U S A 92:758-62. 1995..This observation raises the possibility that mutations involving subunits of other ligand-gated channels may also exist and be the basis of various other neurologic or psychiatric disorders... - Congenital myasthenic syndromesAndrew G Engel
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, Minnesota 55905, USA
Adv Neurol 88:203-15. 2002 - 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 - [Electron transfer flavoprotein in mitochondria]Kinji Ohno
Department of Neurology, Mayo Clinic, USA
Nippon Rinsho 60:113-7. 2002 - 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.... - [Respiratory arrests caused by congenital myasthenia gravis syndrome]Roger F Byring
Vaasan keskussairaala 65130 Vaasa
Duodecim 118:2323-6. 2002 - 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... - 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... - [RNA pathologies in neurological disorders]Kinji Ohno
Division of Neurogenetics and Bioinformatics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine
Rinsho Shinkeigaku 47:801-4. 2007..Potential therapeutic modalities targeting RNA are addressed on congenital myasthenic syndromes, Duchenne muscular dystrophy, spinal muscular atrophy, and familial dysautonomia... - Human branch point consensus sequence is yUnAyKaiping Gao
Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya 466 8550, Japan
Nucleic Acids Res 36:2257-67. 2008..Our analysis demonstrates that the human BPSs are more degenerative than we have expected and that the human BPSs are likely to be recognized in combination with the polypyrimidine tract and/or the other splicing cis-elements... - Congenital myasthenic syndromes:gene mutationsKinji Ohno
Neuromuscul Disord 13:854-7. 2003 - In vitro and in silico analysis reveals an efficient algorithm to predict the splicing consequences of mutations at the 5' splice sitesKentaro Sahashi
Division of Neurogenetics and Bioinformatics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan
Nucleic Acids Res 35:5995-6003. 2007..8, 88.8 and 96.8% of these mutations would affect pre-mRNA splicing, respectively. We propose that the SD-Score algorithm is a practical tool to predict splicing consequences of mutations affecting the 5' splice site...