Congenital myasthenic syndromes: Multiple molecular targets at the neuromuscular junction

Annals of the New York Academy of Sciences

Volumn 998, Issue , 2003, Pages 138-160

  Engel, Andrew G ^a   Ohno, Kinji ^a   Shen, Xin Ming ^a   Sine, Steven M ^a  

^a MAYO CLINIC   (United States)

Author keywords

Acetylcholine receptor (AChR); Acetylcholinesterase; Choline acetyltransferase; Congenital myasthenic syndromes (CMS); Neuromuscular junction; Patch clamp recordings; Rapsyn

Indexed keywords

CHOLINE ACETYLTRANSFERASE; CHOLINERGIC RECEPTOR BLOCKING AGENT; FLUOXETINE; QUINIDINE; SODIUM CHANNEL;

APNEA; BULBAR PARALYSIS; CLINICAL FEATURE; CONFERENCE PAPER; DISEASE SEVERITY; DYSPNEA; ELECTROPHYSIOLOGY; ENDPLATE POTENTIAL; FAST MUSCLE FIBER; FRAMESHIFT MUTATION; GENE EXPRESSION REGULATION; GENETIC ANALYSIS; GENETIC EPISTASIS; GENETIC HETEROGENEITY; HUMAN; INTERCOSTAL MUSCLE; MICROELECTRODE; MISSENSE MUTATION; MYASTHENIA GRAVIS; POINT MUTATION; PROTEIN DOMAIN; SLOW MUSCLE FIBER;

EID: 0141615854     PISSN: 00778923     EISSN: None     Source Type: Book Series    
DOI: 10.1196/annals.1254.016     Document Type: Conference Paper

References (106)

1. OHNO, K., D.O. HUTCHINSON, M. MILONE et al. 1995. Congenital myasthenic syndrome caused by prolonged acetylcholine receptor channel openings due to a mutation in the M2 domain of the ε subunit. Proc. Natl. Acad. Sci. USA 92: 758-762.
2. ENGEL, A.G., K. OHNO, C. BOUZAT et al. 1996. End-plate acetylcholine receptor deficiency due to nonsense mutations in the ε subunit. Ann. Neurol. 40: 810-817.
3. OHNO, K., P. QUIRAM, M. MILONE et al. 1997. Congenital myasthenic syndromes due to heteroallelic nonsense/missense mutations in the acetylcholine receptor ε subunit gene: identification and functional characterization of six new mutations. Hum. Mol. Genet. 6: 753-766.
4. OHNO, K., A.G. ENGEL, X-M. SHEN et al. 2002. Rapsyn mutations in humans cause endplate acetylcholine receptor deficiency and myasthenic syndrome. Am. J. Hum. Genet. 70: 875-885.
5. OHNO, K., J.M. BRENGMAN, A. TSUJINO & A.G. ENGEL. 1998. Human endplate acetylcholinesterase deficiency caused by mutations in the collagen-like tail subunit (ColQ) of the asymmetric enzyme. Proc. Natl. Acad. Sci. USA 95: 9654-9659.
6. OHNO, K., A. TSUJINO, J.M. BRENGMAN et al. 2001. Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. Proc. Natl. Acad. Sci. USA 98: 2017-2022.
7. (a) ENGEL, A.G., K. OHNO & S.M. SINE. 1999. Congenital myasthenic syndromes. In Myasthenia Gravis and Myasthenic Disorders, pp. 251-297. Oxford University Press. London/New York;
8. (b) OHNO, K., M. SADEH, I. BLATT et al. 2003. E-box mutations in RAPSN promoter region in eight cases with congenital myasthenic syndrome. Hum. Mol. Genet. 12: 739-748.
9. KARCAGI, V., I. TOURNEY, A. HERCEGFALVI et al. 2001. Congenital myasthenic syndromes in South-Eastern European Roma (Gypsies). Acta Myol. 20: 231-237.
10. OHNO, K., B. ANLAR, E. ÖZDIRIM et al. 1998. Myasthenic syndromes in Turkish kinships due to mutations in the acetylcholine receptor. Ann. Neurol. 44: 234-241.
11. MIDDLETON, L., K. OHNO, K. CHRISTODOULOU et al. 1999. Congenital myasthenic syndromes linked to chromosome 17p are caused by defects in acetylcholine receptor subunit gene. Neurology 53: 1076-1082.
12. BYRING, R.F., H. PIHKO, X-M. SHEN et al. 2002. Congenital myasthenic syndrome associated with epsiodic apnea and sudden infant death. Neuromuscul. Disord. 12: 548-553.
13. MORA, M., E.H. LAMBERT & A.G. ENGEL. 1987. Synaptic vesicle abnormality in familial infantile myasthenia. Neurology 37: 206-214.
14. HART, Z., K. SAHASHI, E.H. LAMBERT et al. 1979. A congenital, familial, myasthenic syndrome caused by a presynaptic defect of transmitter resynthesis of mobilization [abstract]. Neurology 29: 559.
15. ENGEL, A.G. & E.H. LAMBERT. 1987. Congenital myasthenic syndromes. Electroencephalogr. Clin. Neurophysiol. Suppl. 39: 91-102.
16. HARPER, C.M. 2002. Electrodiagnosis of endplate disease. In Myasthenia Gravis and Myasthenic Disorders, pp. 65-84. Oxford University Press. London/New York.
17. ROBERTSON, W.C., R.W.M. CHUN & S.E. KORNGUTH. 1980. Familial infantile myasthenia. Arch. Neurol. 37: 117-119.
18. OKUDA, T., T. HAGA, Y. KANAI et al. 2000. Identification and characterization of the high-affinity choline transporter. Nat. Neurosci. 3: 120-125.
19. APPARSUNDARAM, S., S.M. FERGUSON, A.L. GEORGE, JR. & R.D. BLAKELY. 2000. Molecular cloning of a human, hemicholinium-3-sensitive choline transporter. Biochem. Biophys. Res. Commun. 276: 862-867.
20. ODA, Y., I. NAKANISHI & T. DEGUCHI. 1992. A complementary DNA for human choline acetyltransferase induces two forms of enzyme with different molecular weights in cultured cells. Brain Res. Mol. Brain Res. 16: 287-294.
21. ERICKSON, J.D., H. VAROQUI, L.E. EIDEN et al. 1994. Functional identification of a vesicular acetylcholine transporter and its expression from a "cholinergic" gene locus. J. Biol. Chem. 269: 21929-21932.
22. REIMER, R.J., A.E. FON & R.H. EDWARDS. 1998. Vesicular neurotransmitter transport and the presynaptic regulation of quantal size. Curr. Opin. Neurobiol. 8: 405-412.
23. EIDEN, L.E. 1998. The cholinergic gene locus. J. Neurochem. 70: 2227-2240.
24. ENGEL, A.G., E.H. LAMBERT & M.R. GOMEZ. 1977. A new myasthenic syndrome with end-plate acetylcholinesterase deficiency, small nerve terminals, and reduced acetylcholine release. Ann. Neurol. 1: 315-330.
25. HUTCHINSON, D.O., T.J. WALLS, S. NAKANO et al. 1993. Congenital endplate acetylcholinesterase deficiency. Brain 116: 633-653.
26. OHNO, K., A.G. ENGEL, J.M. BRENGMAN et al. 2000. The spectrum of mutations causing endplate acetylcholinesterase deficiency. Ann. Neurol. 47: 162-170.
27. KATZ, B. & R. MILEDI. 1973. The binding of acetylcholine to receptors and its removal from the synaptic cleft. J. Physiol. (Lond.) 231: 549-574.
28. KATZ, B. & S. THESLEFF. 1957. A study of the " desensitization" produced by acetyl-choline at the motor end-plate. J. Physiol. (Lond.) 138: 63-80.
29. MASELLI, R.A. & B.C. SOLIVEN. 1991. Analysis of the organophosphate-induced electromyographic response to repetitive nerve stimulation: paradoxical response to edrophonium and d-tubocurarine. Muscle Nerve 14: 1182-1188.
30. SALPETER, M.M., H. KASPRZAK, H. FENG & H. FERTUCK. 1979. End-plates after esterase inactivation in vivo: correlation between esterase concentration, functional response and fine structure. J. Neurocytol. 8: 95-115.
31. DONGER, C., E. KREJCI, P. SERRADELL et al. 1998. Mutation in the human acetylcholinesterase-associated gene, COLQ, is responsible for congenital myasthenic syndrome with end-plate acetylcholinesterase deficiency. Am. J. Hum. Genet. 63: 967-975.
32. SHAPIRA, Y.A., M.E. SADEH, M.P. BERGTRAUM et al. 2002. The novel COLQ mutations and variation of phenotypic expressivity due to G240X. Neurology 58: 603-609.
33. BON, S., F. COUSSEN & J. MASSOULIÉ. 1997. Quaternary associations of acetylcholinesterase. II. The polyproline attachment domain of the collagen tail. J. Biol. Chem. 272: 3016-3021.
34. DEPREZ, P.N. & N.C. INESTROSA. 1995. Two heparin-binding domains are present on the collagenic tail of asymmetric acetylcholinesterase. J. Biol. Chem. 270: 11043-11046.
35. KIMBELL, L.M., K. OHNO, R.L. ROTUNDO & A.G. ENGEL. 2001. Transplanting mutant human collagenic tailed acetylcholinesterase onto the frog neuromuscular junction: evidence for an attachment defect in a congenital myasthenic syndrome [abstract]. Mol. Biol. Cell (Suppl.) 12: 161a.
36. PROCKOP, D.J. & K.I. KIVIRIKKO. 1995. Collagens: molecular biology, diseases, and potentials for therapy. Annu. Rev. Biochem. 64: 403-434.
37. OHNO, K., J.M. BRENGMAN, K.J. FELICE et al. 1999. Congenital endplate acetylcholinesterase deficiency caused by a nonsense mutation and an A-to-G splice site mutation at position +3 of the collagen-like tail subunit gene (COLQ): how does G at position +3 result in aberrant splicing? Am. J. Hum. Genet. 65: 635-644.
38. ISHIGAKI, K., D. NICOLLE, E. KREJCI et al. 2001. Two novel mutations in the ColQ gene causing endplate acetylcholinesterase deficiency [abstract]. Neuromuscul. Disord. 11: 666-667.
39. ENGEL, A.G., K. OHNO, M. MILONE et al. 1996. New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome. Hum. Mol. Genet. 5: 1217-1227.
40. MILONE, M., H-L. WANG, K. OHNO et al. 1997. Slow-channel syndrome caused by enhanced activation, desensitization, and agonist binding affinity due to mutation in the M2 domain of the acetylcholine receptor alpha subunit. J. Neurosci. 17: 5651-5665.
41. ZHOU, M., A.G. ENGEL & A. AUERBACH. 1999. Serum choline activates mutant acetylcholine receptors that cause slow channel congenital myasthenic syndrome. Proc. Natl. Acad. Sci. USA 96: 10466-10471.
42. ENGEL, A.G., E.H. LAMBERT, D.M. MULDER et al. 1982. A newly recognized congenital myasthenic syndrome attributed to a prolonged open time of the acetylcholine-induced ion channel. Ann. Neurol. 11: 553-569.
43. SINE, S.M., K. OHNO, C. BOUZAT et al. 1995. Mutation of the acetylcholine receptor α subunit causes a slow-channel myasthenic syndrome by enhancing agonist binding affinity. Neuron 15: 229-239.
44. WANG, H-L., A. AUERBACH, N. BREN et al. 1997. Mutation in the M1 domain of the acetylcholine receptor alpha subunit decreases the rate of agonist dissociation. J. Gen. Physiol. 109: 757-766.
45. GOMEZ, C.M., R. MASELLI, J. GAMMACK et al. 1996. A beta-subunit mutation in the acetylcholine receptor gate causes severe slow-channel syndrome. Ann. Neurol. 39: 712-723.
46. CROXEN, R., C. NEWLAND, D. BEESON et al. 1997. Mutations in different functional domains of the human muscle acetylcholine receptor α subunit in patients with the slow-channel congenital myasthenic syndrome. Hum. Mol. Genet. 6: 767-774.
47. OHNO, K., M. MILONE, J.M. BRENGMAN et al. 1998. Slow-channel congenital myasthenic syndrome caused by a novel mutation in the acetylcholine receptor ε subunit [abstract]. Neurology 50: A432.
48. OHNO, K., H-L. WANG, X-M. SHEN et al. 2000. Slow-channel mutations in the center of the M1 transmembrane domain of the acetylcholine receptor α subunit [abstract]. Neurology 54(suppl. 3): A183.
49. GOMEZ, C.M., R. MASELLI, J. STAUB et al. 1998. Novel δ and β subunit acetylcholine receptor mutations in the slow-channel syndrome demonstrate phenotypic variability [abstract]. Soc. Neurosci. Abstr. 24: 484.
50. GOMEZ, C.M., R. MASELLI, B.P.S. VOHRA et al. 2002. Novel delta subunit mutation in slow-channel syndrome causes severe weakness by novel mechanism. Ann. Neurol. 51: 102-112.
51. CROXEN, R., C. HATTON, C. SHELLEY et al. 2002. Recessive inheritance and variable penetrance of slow-channel congenital myasthenic syndromes. Neurology 59: 162-168.
52. GROSMAN, C., F.N. SALAMONE, S.M. SINE & A. AUERBACH. 2000. The extracellular linker of muscle acetylcholine receptor channels is a gating control element. J. Gen. Physiol. 116: 327-339.
53. SIEB, J.P., M. MILONE & A.G. ENGEL. 1996. Effects of the quinoline derivatives quinine, quinidine, and chloroquine on neuromuscular transmission. Brain. Res. 712: 179-189.
54. FUKUDOME, T., K. OHNO, J.M. BRENGMAN & A.G. ENGEL. 1998. Quinidine normalizes the open duration of slow-channel mutants of the acetylcholine receptor. Neuroreport 9: 1907-1911.
55. HARPER, C.M. & A.G. ENGEL. 1998. Quinidine sulfate therapy for the slow-channel congenital myasthenic syndrome. Ann. Neurol. 43: 480-484.
56. HARPER, C.M., A.G. ENGEE, T. FUKUDOME et al. 2003. Treatment of slow channel congenital myasthenic syndrome with fluoxetine. Neurology 60: 1710-1713.
57. WANG, H-L., M. MILONE, K. OHNO et al. 1999. Acetylcholine receptor M3 domain: stereochemical and volume contributions to channel gating. Nat. Neurosci. 2: 226-233.
58. MILONE, M., H-L. WANG, K. OHNO et al. 1998. Mode switching kinetics produced by a naturally occurring mutation in the cytoplasmic loop of the human acetylcholine receptor ε subunit. Neuron 20: 575-588.
59. WANG, H-L., K. OHNO, M. MIEONE et al. 2000. Fundamental gating mechanism of nicotinic receptor channel revealed by mutation causing a congenital myasthenic syndrome. J. Gen. Physiol. 116: 449-460.
60. OHNO, K., H-L. WANG, M. MILONE et al. 1996. Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor ε subunit. Neuron 17: 157-170.
61. SHEN, X-M., K. OHNO, M. MILONE et al. 2001. Fast-channel syndrome [abstract]. Neurology 56(suppl. 3): A60.
62. SHEN, X-M., A. TSUJINO, K. OHNO et al. 2000. A novel fast-channel congenital myasthenic syndrome caused by a mutation in the Cys-loop domain of the acetylcholine receptor ε subunit [abstract]. Neurology 54(suppl. 3): A138.
63. BROWNLOW, S., R. WEBSTER, R. CROXEN et al. 2001. Acetylcholine receptor δ subunit mutations underlie a fast-channel myasthenic syndrome and arthrogryposis multiplex congenita. J. Clin. Invest. 108: 125-130.
64. SHEN, X-M., K. OHNO, T. FUKUDOME et al. 1999. Deletion of a single codon from the long cytoplasmic loop of the nAChR subunit gene causes brief single channel currents [abstract]. Soc. Neurosci. Abstr. 25: 1721.
65. SINE, S.M., H-L. WANG, K. OHNO et al. 2003. Mechanistic diversity underlying fast channel congenital myasthenic syndromes. This volume.
66. MILONE, M., K. OHNO, J.N. PRUITT et al. 1996. Congenital myasthenic syndrome due to frameshifting acetylcholine receptor epsilon subunit mutation. Soc. Neurosci. Abstr. 22: 1942-1942.
67. CROXEN, R., C. YOUNG, C. SLATER et al. 2001. Endplate γ and ε subunit mRNA levels in AChR deficiency syndrome due to ε subunit null mutations. Brain 124: 1362-1372.
68. OHNO, K., B. ANLAR & A.G. ENGEE. 1999. Congenital myasthenic syndrome caused by a mutation in the Ets-binding site of the promoter region of the acetylcholine receptor ε subunit gene. Neuromuscul. Disord. 9: 131-135.
69. NICHOLS, P.R., R. CROXEN, A. VINCENT et al. 1999. Mutation of the acetylcholine receptor ε-subunit promoter in congenital myasthenic syndrome. Ann. Neurol. 45: 439-443.
70. ABICHT, A., R. STUCKA, C. SCHMIDT et al. 2002. A newly identified chromosomal microdeletion and an N-box mutation of the AChRε gene cause a congenital myasthenic syndrome. Brain 125: 1005-1013.
71. QUIRAM, P., K. OHNO, M. MILONE et al. 1999. Mutation causing congenital myasthenia reveals acetylcholine receptor β/δ subunit interaction essential for assembly. J. Clin. Invest. 104: 1403-1410.
72. CROXEN, R., C. NEWLAND, M. BETTY et al. 1999. Novel functional ε-subunit polypeptide generated by a single nucleotide deletion in acetylcholine receptor deficiency congenital myasthenic syndrome. Ann. Neurol. 46: 639-647.
73. ABICHT, A., R. STUCKA, V. KARCAGI et al. 1999. A common mutation (ε1267delG) in congenital myasthenic patients of Gipsy ethnic origin. Neurology 53: 1564-1569.
74. HARPER, C.M. & A.G. ENGEL. 2000. Treatment of 31 congenital myasthenic syndrome patients with 3,4-diaminopyridine [abstract]. Neurology 54(suppl. 3): A395.
75. GAUTAM, M., P.G. NOAKES, L. MOSCOSO et al. 1996. Defective neuromuscular synaptogenesis in agrin-deficient mutant mice. Cell 85: 525-535.
76. MITTAUD, P., A. MARANGI, S. ERB-VÖGTLI & C. FUHRER. 2001. Agrin-induced activation of acetylcholine receptor-bound Src family kinases requires rapsyn and correlates with acetylcholine receptor clustering. J. Biol. Chem. 276: 14505-14513.
77. GLASS, D.J., D.C. BOWEN, T.N. STITT et al. 1996. Agrin acts via MuSK receptor complex. Cell 85: 513-523.
78. GAUTAM, M., P.G. NOAKES, J. MUDD et al. 1995. Failure of postsynaptic specialization to develop at neuromuscular junctions of rapsyn-deficient mice. Nature 377: 232-236.
79. APEL, E.D., D.J. GLASS, L.M. MOSCOSCO et al. 1997. Rapsyn is required for MuSK signaling and recruits synaptic components to a MuSK-containing scaffold. Neuron 18: 623-625.
80. RAMARAO, M.K. & J.B. COHEN. 1998. Mechanism of nicotinic acetylcholine receptor cluster formation by rapsyn. Proc. Natl. Acad. Sci. USA 95: 4007-4012.
81. SANDROCK, A.W., S.E. DRYER, K.M. ROSEN et al. 1997. Maintenance of acetylcholine receptor number by neuregulins at the neuromuscular junction in vivo. Science 276: 599-603.
82. SI, J., Z. LUO & L. MEI. 1996. Induction of acetylcholine receptor gene expression by ARIA requires activation of mitogen-activated protein kinase. J. Biol. Chem. 271: 19752-19759.
83. ALTIOK, N., K. ALTIOK & J-P. CHANGEUX. 1997. Heregulin-stimulated acetylcholine receptor gene expression in muscle - requirement for MAP kinase and evidence for parallel inhibitory pathway independent electrical activity. EMBO J. 16: 717-725.
84. NEWEY, S.A., A.O. GRAMOLINI, J. WU, et al. 2001. A novel mechanism for modulating synaptic gene expression: differential localization of α-dystrobrevin transcripts in skeletal muscle. Mol. Cell. Neurosci. 17: 127-140.
85. GRADY, R.M., J.P. MERLIE & J.R. SANES. 1997. Subtle neuromuscular defects in utrophin-deficient mice. J. Cell Biol. 136: 871-882.
86. ADAMS, M.E., M. KRAMARCY, S.P. KRALL et al. 2000. Absence of α-syntrophin leads to structurally aberrant neuromuscular synapses deficient in utrophin. J. Cell Biol. 150: 1385-1398.
87. RAMARAO, M.K., M.J. BIANCHETTA, J. LANKEN & J.B. COHEN. 2001. Role of rapsyn tetratrichopeptide repeat and coiled-coil domains in self-association and nicotinic acetylcholine receptor clustering. J. Biol. Chem. 276: 7475-7483.
88. BARTOLI, M. & J.B. COHEN. 2001. Identification of the modular domains of rapsyn binding to nicotinic acetylcholine receptor (AChR) and to dystroglycan [abstract]. Soc. Neurosci. Abstr. 27: 904.16.
89. BARTOLI, M., M.K. RAMARAO & J.B. COHEN. 2001. Interactions of the rapsyn RING-H2 domain with dystroglycan. J. Biol. Chem. 276: 24911-24917.
90. TSENG, C.N., Y. YAO, J.M. WANG et al. 2001. A synaptic isoform of NRAP interacts with the postsynaptic 43K protein rapsyn and links it to the cytoskeleton at the neuromuscular junction. Soc. Neurosci. Abstr. 27: 694.6.
91. MASELLI, R., M. CHEN, T-Y. CHEN et al. 2002. A heteroallelic nonsense/missense mutation in the acetylcholine receptor α-subunit causing severe endplate AChR deficiency [abstract]. Neurology 58(suppl. 3): A230.
92. MILONE, M., X-M. SHEN, K. OHNO et al. 1999. Unusual congenital myasthenic syndrome with endplate AChR deficiency caused by alpha subunit mutations and a remitting-relapsing course [abstract]. Neurology 52(suppl. 2): 185-186.
93. OHNO, K., X-M. SHEN, T. FUKUDOME et al. 2001. First report of acetylcholine receptor δ subunit mutation causing endplate AChR deficiency [abstract]. Neurology 56(suppl. 3): 232-233.
94. ABICHT, A., R. STUCKA, I-H. SONG et al. 2000. Genetic analysis of the entire AChR ε-subunit gene in 52 congenital myasthenic families. Acta Myol. 19: 23-27.
95. OHNO, K., A.G. ENGEL, M. MILONE et al. 1995. A congenital myasthenic syndrome with severe acetylcholine receptor deficiency caused by heteroallelic frameshifting mutations in the epsilon subunit [abstract]. Neurology 45(suppl. 4): A283.
96. CROXEN, R., J. NEWSOM-DAVIS & D. BEESON. 2000. Endplate acetylcholine receptor deficiency syndrome: two new mutations. Acta Myol. 19: 45-48.
97. BRENGMAN, J.M., K. OHNO, M. MILONE et al. 2000. Identification and functional characterization of eight novel acetylcholine receptor mutations in six congenital myasthenic syndrome kinships [abstract]. Neurology 54(suppl. 3): A182-A183.
98. MASELLI, R.A., M. CHEN, T-Y. CHEN et al. 2002. Severe low-affinity fast-channel syndrome due to a heteroallelic nonsense/missense mutation in the acetylcholine receptor ε-subunit [abstract]. Neurology 58(suppl. 3): A228.
99. SIEB, J.P., S. KRANER, M. RAUCH & O.K. STEINLEIN. 2000. Immature end-plates and utrophin deficiency in congenital myasthenic syndrome caused by epsilon-AChR subunit truncating mutations. Hum. Genet. 107: 160-464.
100. OHNO, K., T. FUKUDOME, S. NAKANO et al. 1996. Mutational analysis in a congenital myasthenic syndrome reveals a novel acetylcholine receptor epsilon subunit mutation. Soc. Neurosci. Abstr. 22: 234-234.
101. BRENGMAN, J.M., K. OHNO, X-M. SHEN & A.G. ENGEL. 1998. Congenital myasthenic syndrome due to two novel mutations in the acetylcholine receptor ε subunit gene [abstract]. Muscle Nerve 21(suppl. 7): S120.
102. HERCEGFALVI, A., A. ABICHT, V. KARCAGI & H. LOCHMÜLLER. 2000. Case report: congenital myasthenic syndrome in a Gipsy family showing pseudodominant pattern of inheritance. Acta Myol. 19: 49-51.
103. SIEB, J.P., S. KRANER, B. SCHRANK et al. 2000. Severe congenital myasthenic syndrome due to homozygosity of the 1293insG epsilon-acetylcholine receptor subunit mutation. Ann. Neurol. 48: 379-383.
104. DEYMEER, F., P. SERDAROGLU, Y. GÜLSEN-PARMAN et al. 2000. Clinical characteristics of a group of Turkish patients having a benign CMS phenotype with ptosis and marked ophthalmoparesis and mutations in the acetylcholine receptor epsilon subunit gene. Acta Myol. 19: 29-32.
105. OHNO, K., A. TSUJINO, B. ANLAR & A.G. ENGEL. 2001. A 16-bp duplication of splice-acceptor site results in silencing of the downstream copy of the splice acceptor site: how are duplicated splice-acceptor sites selected in pre-mRNA splicing? Am. J. Hum. Genet. (Suppl.) 69: 368 [abstract].
106. TSUJINO, A., C. MAERTENS, K. OHNO et al. 2003. Myasthenic syndrome caused by mutation of the SCN4A sodium channel. Proc. Natl. Acad. Sci. USA 100: 7377-7382.