K Ohno

Summary

Affiliation: Mayo Clinic
Country: USA

Publications

  1. pmc Rapsyn mutations in humans cause endplate acetylcholine-receptor deficiency and myasthenic syndrome
    Kinji Ohno
    Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA
    Am J Hum Genet 70:875-85. 2002
  2. ncbi Splicing abnormalities in congenital myasthenic syndromes
    Kinji Ohno
    Division of Neurogenetics and Bioinformatics, Department of Advanced Medical Science, Nagoya University Graduate School of Medicine, Japan
    Acta Myol 24:50-4. 2005
  3. ncbi E-box mutations in the RAPSN promoter region in eight cases with congenital myasthenic syndrome
    Kinji Ohno
    Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA
    Hum Mol Genet 12:739-48. 2003
  4. pmc Lack of founder haplotype for the rapsyn N88K mutation: N88K is an ancient founder mutation or arises from multiple founders
    K Ohno
    Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA
    J Med Genet 41:e8. 2004
  5. ncbi Congenital myasthenic syndromes: genetic defects of the neuromuscular junction
    Kinji 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
  6. ncbi A frameshifting mutation in CHRNE unmasks skipping of the preceding exon
    Kinji Ohno
    Department of Neurology, Mayo Clinic, Rochester, MN, USA
    Hum Mol Genet 12:3055-66. 2003
  7. ncbi Congenital myasthenic syndrome caused by low-expressor fast-channel AChR delta subunit mutation
    X M Shen
    Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA
    Neurology 59:1881-8. 2002
  8. pmc Mutation causing congenital myasthenia reveals acetylcholine receptor beta/delta subunit interaction essential for assembly
    P A Quiram
    Receptor Biology Laboratory, Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Clin Invest 104:1403-10. 1999
  9. ncbi Congenital myasthenic syndromes due to heteroallelic nonsense/missense mutations in the acetylcholine receptor epsilon subunit gene: identification and functional characterization of six new mutations
    K Ohno
    Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic and Foundation, Rochester, MN 55905, USA
    Hum Mol Genet 6:753-66. 1997
  10. ncbi New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome
    A G Engel
    Department of Neurology, Mayo Clinic and Foundation, Rochester, MN 55905, USA
    Hum Mol Genet 5:1217-27. 1996

Collaborators

Detail Information

Publications47

  1. pmc Rapsyn mutations in humans cause endplate acetylcholine-receptor deficiency and myasthenic syndrome
    Kinji 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...
  2. ncbi Splicing abnormalities in congenital myasthenic syndromes
    Kinji 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...
  3. ncbi E-box mutations in the RAPSN promoter region in eight cases with congenital myasthenic syndrome
    Kinji 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...
  4. pmc Lack of founder haplotype for the rapsyn N88K mutation: N88K is an ancient founder mutation or arises from multiple founders
    K Ohno
    Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA
    J Med Genet 41:e8. 2004
  5. ncbi Congenital myasthenic syndromes: genetic defects of the neuromuscular junction
    Kinji 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...
  6. ncbi A frameshifting mutation in CHRNE unmasks skipping of the preceding exon
    Kinji 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...
  7. ncbi Congenital myasthenic syndrome caused by low-expressor fast-channel AChR delta subunit mutation
    X 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...
  8. pmc Mutation causing congenital myasthenia reveals acetylcholine receptor beta/delta subunit interaction essential for assembly
    P 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...
  9. ncbi Congenital myasthenic syndromes due to heteroallelic nonsense/missense mutations in the acetylcholine receptor epsilon subunit gene: identification and functional characterization of six new mutations
    K 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...
  10. ncbi New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome
    A 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...
  11. pmc Fundamental gating mechanism of nicotinic receptor channel revealed by mutation causing a congenital myasthenic syndrome
    H 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...
  12. ncbi Acetylcholine receptor M3 domain: stereochemical and volume contributions to channel gating
    H 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...
  13. pmc 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...
  14. pmc Spectrum of splicing errors caused by CHRNE mutations affecting introns and intron/exon boundaries
    K 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...
  15. ncbi 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 subunit
    M Milone
    Muscle Research Laboratory, Department of Neurology, Mayo Foundation, Rochester, Minnesota 55905, USA
    J Neurosci 17:5651-65. 1997
    ....
  16. ncbi The spectrum of mutations causing end-plate acetylcholinesterase deficiency
    K Ohno
    Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
    Ann Neurol 47:162-70. 2000
    ....
  17. pmc Myasthenic syndrome due to defects in rapsyn: Clinical and molecular findings in 39 patients
    M 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...
  18. ncbi End-plate acetylcholine receptor deficiency due to nonsense mutations in the epsilon subunit
    A 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...
  19. ncbi Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor epsilon subunit
    K 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...
  20. ncbi Mutation of the acetylcholine receptor alpha subunit causes a slow-channel myasthenic syndrome by enhancing agonist binding affinity
    S 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...
  21. pmc Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans
    K 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
    ....
  22. ncbi Subunit-specific contribution to agonist binding and channel gating revealed by inherited mutation in muscle acetylcholine receptor M3-M4 linker
    Xin 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...
  23. pmc Human endplate acetylcholinesterase deficiency caused by mutations in the collagen-like tail subunit (ColQ) of the asymmetric enzyme
    K 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
    ....
  24. pmc Mutation causing severe myasthenia reveals functional asymmetry of AChR signature cystine loops in agonist binding and gating
    Xin 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...
  25. pmc Myasthenic syndrome caused by plectinopathy
    D 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...
  26. ncbi Congenital myasthenic syndromes: A diverse array of molecular targets
    Andrew G Engel
    Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905
    J Neurocytol 32:1017-37. 2003
    ....
  27. ncbi Myofibrillar myopathy: clinical, morphological and genetic studies in 63 patients
    Duygu 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...
  28. ncbi The spectrum of congenital myasthenic syndromes
    Andrew 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...
  29. ncbi Congenital myasthenic syndromes: multiple molecular targets at the neuromuscular junction
    Andrew 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...
  30. ncbi Mechanistic diversity underlying fast channel congenital myasthenic syndromes
    Steven 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...
  31. pmc Naturally occurring mutations at the acetylcholine receptor binding site independently alter ACh binding and channel gating
    Steven 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...
  32. pmc Myasthenic syndrome caused by mutation of the SCN4A sodium channel
    Akira 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...
  33. ncbi Sleuthing molecular targets for neurological diseases at the neuromuscular junction
    Andrew G Engel
    Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, Minnesota 55905, USA
    Nat Rev Neurosci 4:339-52. 2003
  34. ncbi Congenital myasthenic syndromes: progress over the past decade
    Andrew 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...
  35. pmc Congenital myasthenia-related AChR delta subunit mutation interferes with intersubunit communication essential for channel gating
    Xin 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...
  36. pmc Congenital myasthenic syndrome caused by prolonged acetylcholine receptor channel openings due to a mutation in the M2 domain of the epsilon subunit
    K 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...
  37. ncbi Congenital myasthenic syndromes
    Andrew G Engel
    Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, Minnesota 55905, USA
    Adv Neurol 88:203-15. 2002
  38. ncbi Congenital myasthenic syndromes
    Kinji 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
  39. ncbi [Electron transfer flavoprotein in mitochondria]
    Kinji Ohno
    Department of Neurology, Mayo Clinic, USA
    Nihon Rinsho 60:113-7. 2002
  40. ncbi Novel truncating RAPSN mutations causing congenital myasthenic syndrome responsive to 3,4-diaminopyridine
    Brenda L Banwell
    Department of Pediatrics Neurology, The Hospital for Sick Children, University of Toronto, Canada
    Neuromuscul Disord 14:202-7. 2004
    ....
  41. ncbi [Respiratory arrests caused by congenital myasthenia gravis syndrome]
    Roger F Byring
    Vaasan keskussairaala 65130 Vaasa
    Duodecim 118:2323-6. 2002
  42. ncbi C-terminal and heparin-binding domains of collagenic tail subunit are both essential for anchoring acetylcholinesterase at the synapse
    Lewis 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...
  43. pmc Choline acetyltransferase structure reveals distribution of mutations that cause motor disorders
    Yiying 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...
  44. ncbi [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...
  45. pmc Human branch point consensus sequence is yUnAy
    Kaiping 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...
  46. ncbi Congenital myasthenic syndromes:gene mutations
    Kinji Ohno
    Neuromuscul Disord 13:854-7. 2003
  47. pmc In vitro and in silico analysis reveals an efficient algorithm to predict the splicing consequences of mutations at the 5' splice sites
    Kentaro 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...