KEGG   DISEASE: Congenital myasthenic syndrome
Entry
H00770                      Disease                                
Name
Congenital myasthenic syndrome
Description
Congenital myasthenic syndromes (CMS) are a heterogenous group of genetic disorders caused by mutations in several proteins that compose the neuromuscular junction (NMJ) apparatus on which synaptic formation and function depend. The majority are recessively inherited. The disorders of the NMJ cause weakness and fatigue.
Category
Nervous system disease
Brite
Human diseases [BR:br08402]
 Nervous system diseases
  Other nervous and sensory system diseases
   H00770  Congenital myasthenic syndrome
Human diseases in ICD-11 classification [BR:br08403]
 08 Diseases of the nervous system
  Diseases of neuromuscular junction or muscle
   Myasthenia gravis or certain specified neuromuscular junction disorders
    8C61  Congenital myasthenic syndromes
     H00770  Congenital myasthenic syndrome
Pathway
hsa04080  Neuroactive ligand-receptor interaction
hsa00510  N-Glycan biosynthesis
hsa04725  Cholinergic synapse
hsa04721  Synaptic vesicle cycle
hsa00513  Various types of N-glycan biosynthesis
Gene
(CMS1A/1B) CHRNA1 [HSA:1134] [KO:K04803]
(CMS2A/2C) CHRNB1 [HSA:1140] [KO:K04812]
(CMS3A/3B/3C) CHRND [HSA:1144] [KO:K04816]
(CMS4A/4B/4C) CHRNE [HSA:1145] [KO:K04817]
(CMS5) COLQ [HSA:8292]
(CMS6) CHAT [HSA:1103] [KO:K00623]
(CMS7A/7B) SYT2 [HSA:127833] [KO:K19902]
(CMS8) AGRN [HSA:375790] [KO:K06254]
(CMS9) MUSK [HSA:4593] [KO:K05129]
(CMS10) DOK7 [HSA:285489] [KO:K24038]
(CMS11) RAPSN [HSA:5913] [KO:K24924]
(CMS12) GFPT1 [HSA:2673] [KO:K00820]
(CMS13) DPAGT1 [HSA:1798] [KO:K01001]
(CMS14) ALG2 [HSA:85365] [KO:K03843]
(CMS15) ALG14 [HSA:199857] [KO:K07441]
(CMS16) SCN4A [HSA:6329] [KO:K04837]
(CMS17) LRP4 [HSA:4038] [KO:K20051]
(CMS18) SNAP25 [HSA:6616] [KO:K18211]
(CMS19) COL13A1 [HSA:1305] [KO:K16617]
(CMS20) SLC5A7 [HSA:60482] [KO:K14387]
(CMS21) SLC18A3 [HSA:6572] [KO:K14636]
(CMS22) PREPL [HSA:9581] [KO:K22582]
(CMS23) SLC25A1 [HSA:6576] [KO:K15100]
(CMS24) MYO9A [HSA:4649] [KO:K10360]
(CMS25) VAMP1 [HSA:6843] [KO:K08510]
Other DBs
ICD-11: 8C61
ICD-10: G70.2
MeSH: D020294
OMIM: 601462 608930 616313 616314 616321 616322 616323 605809 616324 608931 603034 254210 616040 619461 615120 616325 254300 616326 610542 614750 616228 616227 614198 616304 616330 616720 617143 617239 616224 618197 618198 618323
Reference
  Authors
Argov Z
  Title
Management of myasthenic conditions: nonimmune issues.
  Journal
Curr Opin Neurol 22:493-7 (2009)
DOI:10.1097/WCO.0b013e32832f15fa
Reference
  Authors
Spillane J, Beeson DJ, Kullmann DM
  Title
Myasthenia and related disorders of the neuromuscular junction.
  Journal
J Neurol Neurosurg Psychiatry 81:850-7 (2010)
DOI:10.1136/jnnp.2008.169367
Reference
PMID:8872460 (CMS1A CMS2A CMS4A)
  Authors
Engel AG, Ohno K, Milone M, Wang HL, Nakano S, Bouzat C, Pruitt JN 2nd, Hutchinson DO, Brengman JM, Bren N, Sieb JP, Sine SM
  Title
New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome.
  Journal
Hum Mol Genet 5:1217-27 (1996)
DOI:10.1093/hmg/5.9.1217
Reference
PMID:10195214 (CMS1B)
  Authors
Wang HL, Milone M, Ohno K, Shen XM, Tsujino A, Batocchi AP, Tonali P, Brengman J, Engel AG, Sine SM
  Title
Acetylcholine receptor M3 domain: stereochemical and volume contributions to channel gating.
  Journal
Nat Neurosci 2:226-33 (1999)
DOI:10.1038/6326
Reference
PMID:10562302 (CMS2C)
  Authors
Quiram PA, Ohno K, Milone M, Patterson MC, Pruitt NJ, Brengman JM, Sine SM, Engel AG
  Title
Mutation causing congenital myasthenia reveals acetylcholine receptor beta/delta subunit interaction essential for assembly.
  Journal
J Clin Invest 104:1403-10 (1999)
DOI:10.1172/JCI8179
Reference
PMID:11782989 (CMS3A)
  Authors
Gomez CM, Maselli RA, Vohra BP, Navedo M, Stiles JR, Charnet P, Schott K, Rojas L, Keesey J, Verity A, Wollmann RW, Lasalde-Dominicci J
  Title
Novel delta subunit mutation in slow-channel syndrome causes severe weakness by novel mechanisms.
  Journal
Ann Neurol 51:102-12 (2002)
DOI:10.1002/ana.10077
Reference
PMID:11435464 (CMS3B)
  Authors
Brownlow S, Webster R, Croxen R, Brydson M, Neville B, Lin JP, Vincent A, Newsom-Davis J, Beeson D
  Title
Acetylcholine receptor delta subunit mutations underlie a fast-channel myasthenic syndrome and arthrogryposis multiplex congenita.
  Journal
J Clin Invest 108:125-30 (2001)
DOI:10.1172/JCI12935
Reference
PMID:16916845 (CMS3C)
  Authors
Muller JS, Baumeister SK, Schara U, Cossins J, Krause S, von der Hagen M, Huebner A, Webster R, Beeson D, Lochmuller H, Abicht A
  Title
CHRND mutation causes a congenital myasthenic syndrome by impairing co-clustering of the acetylcholine receptor with rapsyn.
  Journal
Brain 129:2784-93 (2006)
DOI:10.1093/brain/awl188
Reference
PMID:8755487 (CMS4B)
  Authors
Ohno K, Wang HL, Milone M, Bren N, Brengman JM, Nakano S, Quiram P, Pruitt JN, Sine SM, Engel AG
  Title
Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor epsilon subunit.
  Journal
Neuron 17:157-70 (1996)
DOI:10.1016/s0896-6273(00)80289-5
Reference
PMID:8957026 (CMS4C)
  Authors
Engel AG, Ohno K, Bouzat C, Sine SM, Griggs RC
  Title
End-plate acetylcholine receptor deficiency due to nonsense mutations in the epsilon subunit.
  Journal
Ann Neurol 40:810-7 (1996)
DOI:10.1002/ana.410400521
Reference
PMID:9689136 (CMS5)
  Authors
Ohno K, Brengman J, Tsujino A, Engel AG
  Title
Human endplate acetylcholinesterase deficiency caused by mutations in the collagen-like tail subunit (ColQ) of the asymmetric enzyme.
  Journal
Proc Natl Acad Sci U S A 95:9654-9 (1998)
DOI:10.1073/pnas.95.16.9654
Reference
PMID:11172068 (CMS6)
  Authors
Ohno K, Tsujino A, Brengman JM, Harper CM, Bajzer Z, Udd B, Beyring R, Robb S, Kirkham FJ, Engel AG
  Title
Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans.
  Journal
Proc Natl Acad Sci U S A 98:2017-22 (2001)
DOI:10.1073/pnas.98.4.2017
Reference
PMID:25192047 (CMS7A)
  Authors
Herrmann DN, Horvath R, Sowden JE, Gonzalez M, Sanchez-Mejias A, Guan Z, Whittaker RG, Almodovar JL, Lane M, Bansagi B, Pyle A, Boczonadi V, Lochmuller H, Griffin H, Chinnery PF, Lloyd TE, Littleton JT, Zuchner S
  Title
Synaptotagmin 2 mutations cause an autosomal-dominant form of lambert-eaton myasthenic syndrome and nonprogressive motor neuropathy.
  Journal
Am J Hum Genet 95:332-9 (2014)
DOI:10.1016/j.ajhg.2014.08.007
Reference
PMID:32250532 (CMS7B)
  Authors
Maselli RA, van der Linden H Jr, Ferns M
  Title
Recessive congenital myasthenic syndrome caused by a homozygous mutation in SYT2 altering a highly conserved C-terminal amino acid sequence.
  Journal
Am J Med Genet A 182:1744-1749 (2020)
DOI:10.1002/ajmg.a.61579
Reference
PMID:19631309 (CMS8)
  Authors
Huze C, Bauche S, Richard P, Chevessier F, Goillot E, Gaudon K, Ben Ammar A, Chaboud A, Grosjean I, Lecuyer HA, Bernard V, Rouche A, Alexandri N, Kuntzer T, Fardeau M, Fournier E, Brancaccio A, Ruegg MA, Koenig J, Eymard B, Schaeffer L, Hantai D
  Title
Identification of an agrin mutation that causes congenital myasthenia and affects synapse function.
  Journal
Am J Hum Genet 85:155-67 (2009)
DOI:10.1016/j.ajhg.2009.06.015
Reference
PMID:15496425 (CMS9)
  Authors
Chevessier F, Faraut B, Ravel-Chapuis A, Richard P, Gaudon K, Bauche S, Prioleau C, Herbst R, Goillot E, Ioos C, Azulay JP, Attarian S, Leroy JP, Fournier E, Legay C, Schaeffer L, Koenig J, Fardeau M, Eymard B, Pouget J, Hantai D
  Title
MUSK, a new target for mutations causing congenital myasthenic syndrome.
  Journal
Hum Mol Genet 13:3229-40 (2004)
DOI:10.1093/hmg/ddh333
Reference
PMID:16917026 (CMS10)
  Authors
Beeson D, Higuchi O, Palace J, Cossins J, Spearman H, Maxwell S, Newsom-Davis J, Burke G, Fawcett P, Motomura M, Muller JS, Lochmuller H, Slater C, Vincent A, Yamanashi Y
  Title
Dok-7 mutations underlie a neuromuscular junction synaptopathy.
  Journal
Science 313:1975-8 (2006)
DOI:10.1126/science.1130837
Reference
PMID:11791205 (CMS11)
  Authors
Ohno K, Engel AG, Shen XM, Selcen D, Brengman J, Harper CM, Tsujino A, Milone M
  Title
Rapsyn mutations in humans cause endplate acetylcholine-receptor deficiency and myasthenic syndrome.
  Journal
Am J Hum Genet 70:875-85 (2002)
DOI:10.1086/339465
Reference
PMID:21310273 (CMS12)
  Authors
Senderek J, Muller JS, Dusl M, Strom TM, Guergueltcheva V, Diepolder I, Laval SH, Maxwell S, Cossins J, Krause S, Muelas N, Vilchez JJ, Colomer J, Mallebrera CJ, Nascimento A, Nafissi S, Kariminejad A, Nilipour Y, Bozorgmehr B, Najmabadi H, Rodolico C, Sieb JP, Steinlein OK, Schlotter B, Schoser B, Kirschner J, Herrmann R, Voit T, Oldfors A, Lindbergh C, Urtizberea A, von der Hagen M, Hubner A, Palace J, Bushby K, Straub V, Beeson D, Abicht A, Lochmuller H
  Title
Hexosamine biosynthetic pathway mutations cause neuromuscular transmission defect.
  Journal
Am J Hum Genet 88:162-72 (2011)
DOI:10.1016/j.ajhg.2011.01.008
Reference
PMID:22742743 (CMS13)
  Authors
Belaya K, Finlayson S, Slater CR, Cossins J, Liu WW, Maxwell S, McGowan SJ, Maslau S, Twigg SR, Walls TJ, Pascual Pascual SI, Palace J, Beeson D
  Title
Mutations in DPAGT1 cause a limb-girdle congenital myasthenic syndrome with tubular aggregates.
  Journal
Am J Hum Genet 91:193-201 (2012)
DOI:10.1016/j.ajhg.2012.05.022
Reference
PMID:23404334 (CMS14 CMS15)
  Authors
Cossins J, Belaya K, Hicks D, Salih MA, Finlayson S, Carboni N, Liu WW, Maxwell S, Zoltowska K, Farsani GT, Laval S, Seidhamed MZ, Donnelly P, Bentley D, McGowan SJ, Muller J, Palace J, Lochmuller H, Beeson D
  Title
Congenital myasthenic syndromes due to mutations in ALG2 and ALG14.
  Journal
Brain 136:944-56 (2013)
DOI:10.1093/brain/awt010
Reference
PMID:12766226 (CMS16)
  Authors
Tsujino A, Maertens C, Ohno K, Shen XM, Fukuda T, Harper CM, Cannon SC, Engel AG
  Title
Myasthenic syndrome caused by mutation of the SCN4A sodium channel.
  Journal
Proc Natl Acad Sci U S A 100:7377-82 (2003)
DOI:10.1073/pnas.1230273100
Reference
PMID:24234652 (CMS17)
  Authors
Ohkawara B, Cabrera-Serrano M, Nakata T, Milone M, Asai N, Ito K, Ito M, Masuda A, Ito Y, Engel AG, Ohno K
  Title
LRP4 third beta-propeller domain mutations cause novel congenital myasthenia by compromising agrin-mediated MuSK signaling in a position-specific manner.
  Journal
Hum Mol Genet 23:1856-68 (2014)
DOI:10.1093/hmg/ddt578
Reference
PMID:25381298 (CMS18)
  Authors
Shen XM, Selcen D, Brengman J, Engel AG
  Title
Mutant SNAP25B causes myasthenia, cortical hyperexcitability, ataxia, and intellectual disability.
  Journal
Neurology 83:2247-55 (2014)
DOI:10.1212/WNL.0000000000001079
Reference
PMID:26626625 (CMS19)
  Authors
Logan CV, Cossins J, Rodriguez Cruz PM, Parry DA, Maxwell S, Martinez-Martinez P, Riepsaame J, Abdelhamed ZA, Lake AV, Moran M, Robb S, Chow G, Sewry C, Hopkins PM, Sheridan E, Jayawant S, Palace J, Johnson CA, Beeson D
  Title
Congenital Myasthenic Syndrome Type 19 Is Caused by Mutations in COL13A1, Encoding the Atypical Non-fibrillar Collagen Type XIII alpha1 Chain.
  Journal
Am J Hum Genet 97:878-85 (2015)
DOI:10.1016/j.ajhg.2015.10.017
Reference
PMID:27569547 (CMS20)
  Authors
Bauche S, O'Regan S, Azuma Y, Laffargue F, McMacken G, Sternberg D, Brochier G, Buon C, Bouzidi N, Topf A, Lacene E, Remerand G, Beaufrere AM, Pebrel-Richard C, Thevenon J, El Chehadeh-Djebbar S, Faivre L, Duffourd Y, Ricci F, Mongini T, Fiorillo C, Astrea G, Burloiu CM, Butoianu N, Sandu C, Servais L, Bonne G, Nelson I, Desguerre I, Nougues MC, Boeuf B, Romero N, Laporte J, Boland A, Lechner D, Deleuze JF, Fontaine B, Strochlic L, Lochmuller H, Eymard B, Mayer M, Nicole S
  Title
Impaired Presynaptic High-Affinity Choline Transporter Causes a Congenital Myasthenic Syndrome with Episodic Apnea.
  Journal
Am J Hum Genet 99:753-761 (2016)
DOI:10.1016/j.ajhg.2016.06.033
Reference
PMID:27590285 (CMS21)
  Authors
O'Grady GL, Verschuuren C, Yuen M, Webster R, Menezes M, Fock JM, Pride N, Best HA, Benavides Damm T, Turner C, Lek M, Engel AG, North KN, Clarke NF, MacArthur DG, Kamsteeg EJ, Cooper ST
  Title
Variants in SLC18A3, vesicular acetylcholine transporter, cause congenital myasthenic syndrome.
  Journal
Neurology 87:1442-1448 (2016)
DOI:10.1212/WNL.0000000000003179
Reference
PMID:24610330 (CMS22)
  Authors
Regal L, Shen XM, Selcen D, Verhille C, Meulemans S, Creemers JW, Engel AG
  Title
PREPL deficiency with or without cystinuria causes a novel myasthenic syndrome.
  Journal
Neurology 82:1254-60 (2014)
DOI:10.1212/WNL.0000000000000295
Reference
PMID:26870663 (CMS23)
  Authors
Chaouch A, Porcelli V, Cox D, Edvardson S, Scarcia P, De Grassi A, Pierri CL, Cossins J, Laval SH, Griffin H, Muller JS, Evangelista T, Topf A, Abicht A, Huebner A, von der Hagen M, Bushby K, Straub V, Horvath R, Elpeleg O, Palace J, Senderek J, Beeson D, Palmieri L, Lochmuller H
  Title
Mutations in the Mitochondrial Citrate Carrier SLC25A1 are Associated with Impaired Neuromuscular Transmission.
  Journal
J Neuromuscul Dis 1:75-90 (2014)
DOI:10.3233/JND-140021
Reference
PMID:27259756 (CMS24)
  Authors
O'Connor E, Topf A, Muller JS, Cox D, Evangelista T, Colomer J, Abicht A, Senderek J, Hasselmann O, Yaramis A, Laval SH, Lochmuller H
  Title
Identification of mutations in the MYO9A gene in patients with congenital myasthenic syndrome.
  Journal
Brain 139:2143-53 (2016)
DOI:10.1093/brain/aww130
Reference
PMID:28253535 (CMS25)
  Authors
Salpietro V, Lin W, Delle Vedove A, Storbeck M, Liu Y, Efthymiou S, Manole A, Wiethoff S, Ye Q, Saggar A, McElreavey K, Krishnakumar SS, Pitt M, Bello OD, Rothman JE, Basel-Vanagaite L, Hubshman MW, Aharoni S, Manzur AY, Wirth B, Houlden H
  Title
Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome.
  Journal
Ann Neurol 81:597-603 (2017)
DOI:10.1002/ana.24905
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