KEGG   DISEASE: Primary dystonia
Entry
H00831                      Disease                                
Name
Primary dystonia
  Subgroup
DOPA-responsive dystonia (DRD) [DS:H02557]
Description
Dystonias are a heterogeneous group of hyperkinetic movement disorders characterized by involuntary sustained muscle contractions that lead to abnormal postures and repetitive movements. Presently, 30 distinct monogenic primary dystonias have been recognized. They can be divided into Primary torsion dystonias (PTDs), dystonia-plus syndromes without brain degeneration, dystonia-parkinsonism with brain degeneration (i.e. DYT3), and paroxysmal dyskinesias.
Category
Nervous system disease
Brite
Human diseases [BR:br08402]
 Nervous system diseases
  Other nervous and sensory system diseases
   H00831  Primary dystonia
Human diseases in ICD-11 classification [BR:br08403]
 08 Diseases of the nervous system
  Movement disorders
   8A02  Dystonic disorders
    H00831  Primary dystonia
Related
pathway
hsa04728  Dopaminergic synapse
hsa04919  Thyroid hormone signaling pathway
hsa04911  Insulin secretion
hsa04976  Bile secretion
hsa04020  Calcium signaling pathway
Gene
(DYT1) TOR1A [HSA:1861] [KO:K22990]
(DYT2) HPCA [HSA:3208] [KO:K23846]
(DYT3) TAF1 [HSA:6872] [KO:K03125]
(DYT4) TUBB4A [HSA:10382] [KO:K07375]
(DYT5) GCH1 [HSA:2643] [KO:K01495]
(DYT6) THAP1 [HSA:55145] [KO:K23203]
(DYT8) PNKD [HSA:25953] [KO:K23864]
(DYT9/DYT18) SLC2A1 [HSA:6513] [KO:K07299]
(DYT10) PRRT2 [HSA:112476] [KO:K23897]
(DYT11) SGCE [HSA:8910]
(DYT12) ATP1A3 [HSA:478] [KO:K01539]
(DYT16) PRKRA [HSA:8575] [KO:K24540]
(DYT23) CACNA1B [HSA:774] [KO:K04849]
(DYT24) ANO3 [HSA:63982] [KO:K19498]
(DYT25) GNAL [HSA:2774] [KO:K04633]
(DYT26) KCTD17 [HSA:79734] [KO:K21914]
(DYT27) COL6A3 [HSA:1293] [KO:K06238]
(DYT28) KMT2B [HSA:9757] [KO:K14959]
(DYT29) MECR [HSA:51102] [KO:K07512]
(DYT30) VPS16 [HSA:64601] [KO:K20180]
(DYT31) AOPEP [HSA:84909] [KO:K09606]
(DYT32) VPS11 [HSA:55823] [KO:K20179]
(DYT33) EIF2AK2 [HSA:5610] [KO:K16195]
(DYT34) KCNN2 [HSA:3781] [KO:K04943]
(DYT35) SHQ1 [HSA:55164] [KO:K14764]
Other DBs
ICD-11: 8A02.0
ICD-10: G24.1
MeSH: D020821
OMIM: 128100 128101 224500 314250 128230 602629 118800 128200 159900 128235 612067 601042 614860 615034 615073 616398 616411 612716 605407 617284 617282 619291 619565 619637 619687 619724 619921
Reference
  Authors
Phukan J, Albanese A, Gasser T, Warner T
  Title
Primary dystonia and dystonia-plus syndromes: clinical characteristics, diagnosis, and pathogenesis.
  Journal
Lancet Neurol 10:1074-85 (2011)
DOI:10.1016/S1474-4422(11)70232-0
Reference
  Authors
Bruggemann N, Klein C
  Title
Genetics of primary torsion dystonia.
  Journal
Curr Neurol Neurosci Rep 10:199-206 (2010)
DOI:10.1007/s11910-010-0107-5
Reference
  Authors
Muller U
  Title
The monogenic primary dystonias.
  Journal
Brain 132:2005-25 (2009)
DOI:10.1093/brain/awp172
Reference
  Authors
Barrett MJ, Bressman S
  Title
Genetics and pharmacological treatment of dystonia.
  Journal
Int Rev Neurobiol 98:525-49 (2011)
DOI:10.1016/B978-0-12-381328-2.00019-5
Reference
PMID:9288096 (TOR1A)
  Authors
Ozelius LJ, Hewett JW, Page CE, Bressman SB, Kramer PL, Shalish C, de Leon D, Brin MF, Raymond D, Corey DP, Fahn S, Risch NJ, Buckler AJ, Gusella JF, Breakefield XO
  Title
The early-onset torsion dystonia gene (DYT1) encodes an ATP-binding protein.
  Journal
Nat Genet 17:40-8 (1997)
DOI:10.1038/ng0997-40
Reference
PMID:25799108 (HPCA)
  Authors
Charlesworth G, Angelova PR, Bartolome-Robledo F, Ryten M, Trabzuni D, Stamelou M, Abramov AY, Bhatia KP, Wood NW
  Title
Mutations in HPCA cause autosomal-recessive primary isolated dystonia.
  Journal
Am J Hum Genet 96:657-65 (2015)
DOI:10.1016/j.ajhg.2015.02.007
Reference
PMID:17273961 (TAF1)
  Authors
Makino S, Kaji R, Ando S, Tomizawa M, Yasuno K, Goto S, Matsumoto S, Tabuena MD, Maranon E, Dantes M, Lee LV, Ogasawara K, Tooyama I, Akatsu H, Nishimura M, Tamiya G
  Title
Reduced neuron-specific expression of the TAF1 gene is associated with X-linked dystonia-parkinsonism.
  Journal
Am J Hum Genet 80:393-406 (2007)
DOI:10.1086/512129
Reference
PMID:23424103 (TUBB4A)
  Authors
Hersheson J, Mencacci NE, Davis M, MacDonald N, Trabzuni D, Ryten M, Pittman A, Paudel R, Kara E, Fawcett K, Plagnol V, Bhatia KP, Medlar AJ, Stanescu HC, Hardy J, Kleta R, Wood NW, Houlden H
  Title
Mutations in the autoregulatory domain of beta-tubulin 4a cause hereditary dystonia.
  Journal
Ann Neurol 73:546-53 (2013)
DOI:10.1002/ana.23832
Reference
PMID:7874165 (GCH1)
  Authors
Ichinose H, Ohye T, Takahashi E, Seki N, Hori T, Segawa M, Nomura Y, Endo K, Tanaka H, Tsuji S, et al.
  Title
Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene.
  Journal
Nat Genet 8:236-42 (1994)
DOI:10.1038/ng1194-236
Reference
PMID:19182804 (THAP1)
  Authors
Fuchs T, Gavarini S, Saunders-Pullman R, Raymond D, Ehrlich ME, Bressman SB, Ozelius LJ
  Title
Mutations in the THAP1 gene are responsible for DYT6 primary torsion dystonia.
  Journal
Nat Genet 41:286-8 (2009)
DOI:10.1038/ng.304
Reference
PMID:15262732 (PNKD)
  Authors
Rainier S, Thomas D, Tokarz D, Ming L, Bui M, Plein E, Zhao X, Lemons R, Albin R, Delaney C, Alvarado D, Fink JK
  Title
Myofibrillogenesis regulator 1 gene mutations cause paroxysmal dystonic choreoathetosis.
  Journal
Arch Neurol 61:1025-9 (2004)
DOI:10.1001/archneur.61.7.1025
Reference
PMID:21832227 (SLC2A1)
  Authors
Weber YG, Kamm C, Suls A, Kempfle J, Kotschet K, Schule R, Wuttke TV, Maljevic S, Liebrich J, Gasser T, Ludolph AC, Van Paesschen W, Schols L, De Jonghe P, Auburger G, Lerche H
  Title
Paroxysmal choreoathetosis/spasticity (DYT9) is caused by a GLUT1 defect.
  Journal
Neurology 77:959-64 (2011)
DOI:10.1212/WNL.0b013e31822e0479
Reference
PMID:22101681 (PRRT2)
  Authors
Chen WJ, Lin Y, Xiong ZQ, Wei W, Ni W, Tan GH, Guo SL, He J, Chen YF, Zhang QJ, Li HF, Lin Y, Murong SX, Xu J, Wang N, Wu ZY
  Title
Exome sequencing identifies truncating mutations in PRRT2 that cause paroxysmal kinesigenic dyskinesia.
  Journal
Nat Genet 43:1252-5 (2011)
DOI:10.1038/ng.1008
Reference
PMID:11528394 (SGCE)
  Authors
Zimprich A, Grabowski M, Asmus F, Naumann M, Berg D, Bertram M, Scheidtmann K, Kern P, Winkelmann J, Muller-Myhsok B, Riedel L, Bauer M, Muller T, Castro M, Meitinger T, Strom TM, Gasser T
  Title
Mutations in the gene encoding epsilon-sarcoglycan cause myoclonus-dystonia syndrome.
  Journal
Nat Genet 29:66-9 (2001)
DOI:10.1038/ng709
Reference
PMID:15260953 (ATP1A3)
  Authors
de Carvalho Aguiar P, Sweadner KJ, Penniston JT, Zaremba J, Liu L, Caton M, Linazasoro G, Borg M, Tijssen MA, Bressman SB, Dobyns WB, Brashear A, Ozelius LJ
  Title
Mutations in the Na+/K+ -ATPase alpha3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism.
  Journal
Neuron 43:169-75 (2004)
DOI:10.1016/j.neuron.2004.06.028
Reference
PMID:18243799 (PRKRA)
  Authors
Camargos S, Scholz S, Simon-Sanchez J, Paisan-Ruiz C, Lewis P, Hernandez D, Ding J, Gibbs JR, Cookson MR, Bras J, Guerreiro R, Oliveira CR, Lees A, Hardy J, Cardoso F, Singleton AB
  Title
DYT16, a novel young-onset dystonia-parkinsonism disorder: identification of a segregating mutation in the stress-response protein PRKRA.
  Journal
Lancet Neurol 7:207-15 (2008)
DOI:10.1016/S1474-4422(08)70022-X
Reference
PMID:25296916 (CACNA1B)
  Authors
Groen JL, Andrade A, Ritz K, Jalalzadeh H, Haagmans M, Bradley TE, Jongejan A, Verbeek DS, Nurnberg P, Denome S, Hennekam RC, Lipscombe D, Baas F, Tijssen MA
  Title
CACNA1B mutation is linked to unique myoclonus-dystonia syndrome.
  Journal
Hum Mol Genet 24:987-93 (2015)
DOI:10.1093/hmg/ddu513
Reference
PMID:23200863 (ANO3)
  Authors
Charlesworth G, Plagnol V, Holmstrom KM, Bras J, Sheerin UM, Preza E, Rubio-Agusti I, Ryten M, Schneider SA, Stamelou M, Trabzuni D, Abramov AY, Bhatia KP, Wood NW
  Title
Mutations in ANO3 cause dominant craniocervical dystonia: ion channel implicated in pathogenesis.
  Journal
Am J Hum Genet 91:1041-50 (2012)
DOI:10.1016/j.ajhg.2012.10.024
Reference
PMID:23222958 (GNAL)
  Authors
Fuchs T, Saunders-Pullman R, Masuho I, Luciano MS, Raymond D, Factor S, Lang AE, Liang TW, Trosch RM, White S, Ainehsazan E, Herve D, Sharma N, Ehrlich ME, Martemyanov KA, Bressman SB, Ozelius LJ
  Title
Mutations in GNAL cause primary torsion dystonia.
  Journal
Nat Genet 45:88-92 (2013)
DOI:10.1038/ng.2496
Reference
PMID:25983243 (KCTD17)
  Authors
Mencacci NE, Rubio-Agusti I, Zdebik A, Asmus F, Ludtmann MH, Ryten M, Plagnol V, Hauser AK, Bandres-Ciga S, Bettencourt C, Forabosco P, Hughes D, Soutar MM, Peall K, Morris HR, Trabzuni D, Tekman M, Stanescu HC, Kleta R, Carecchio M, Zorzi G, Nardocci N, Garavaglia B, Lohmann E, Weissbach A, Klein C, Hardy J, Pittman AM, Foltynie T, Abramov AY, Gasser T, Bhatia KP, Wood NW
  Title
A missense mutation in KCTD17 causes autosomal dominant myoclonus-dystonia.
  Journal
Am J Hum Genet 96:938-47 (2015)
DOI:10.1016/j.ajhg.2015.04.008
Reference
PMID:26004199 (COL6A3)
  Authors
Zech M, Lam DD, Francescatto L, Schormair B, Salminen AV, Jochim A, Wieland T, Lichtner P, Peters A, Gieger C, Lochmuller H, Strom TM, Haslinger B, Katsanis N, Winkelmann J
  Title
Recessive mutations in the alpha3 (VI) collagen gene COL6A3 cause early-onset isolated dystonia.
  Journal
Am J Hum Genet 96:883-93 (2015)
DOI:10.1016/j.ajhg.2015.04.010
Reference
PMID:27992417 (KMT2B)
  Authors
Meyer E, Carss KJ, Rankin J, Nichols JM, Grozeva D, Joseph AP, Mencacci NE, Papandreou A, Ng J, Barral S, Ngoh A, Ben-Pazi H, Willemsen MA, Arkadir D, Barnicoat A, Bergman H, Bhate S, Boys A, Darin N, Foulds N, Gutowski N, Hills A, Houlden H, Hurst JA, Israel Z, Kaminska M, Limousin P, Lumsden D, McKee S, Misra S, Mohammed SS, Nakou V, Nicolai J, Nilsson M, Pall H, Peall KJ, Peters GB, Prabhakar P, Reuter MS, Rump P, Segel R, Sinnema M, Smith M, Turnpenny P, White SM, Wieczorek D, Wiethoff S, Wilson BT, Winter G, Wragg C, Pope S, Heales SJ, Morrogh D, Pittman A, Carr LJ, Perez-Duenas B, Lin JP, Reis A, Gahl WA, Toro C, Bhatia KP, Wood NW, Kamsteeg EJ, Chong WK, Gissen P, Topf M, Dale RC, Chubb JR, Raymond FL, Kurian MA
  Title
Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia.
  Journal
Nat Genet 49:223-237 (2017)
DOI:10.1038/ng.3740
Reference
PMID:27817865 (MECR)
  Authors
Heimer G, Keratar JM, Riley LG, Balasubramaniam S, Eyal E, Pietikainen LP, Hiltunen JK, Marek-Yagel D, Hamada J, Gregory A, Rogers C, Hogarth P, Nance MA, Shalva N, Veber A, Tzadok M, Nissenkorn A, Tonduti D, Renaldo F, Kraoua I, Panteghini C, Valletta L, Garavaglia B, Cowley MJ, Gayevskiy V, Roscioli T, Silberstein JM, Hoffmann C, Raas-Rothschild A, Tiranti V, Anikster Y, Christodoulou J, Kastaniotis AJ, Ben-Zeev B, Hayflick SJ
  Title
MECR Mutations Cause Childhood-Onset Dystonia and Optic Atrophy, a Mitochondrial Fatty Acid Synthesis Disorder.
  Journal
Am J Hum Genet 99:1229-1244 (2016)
DOI:10.1016/j.ajhg.2016.09.021
Reference
PMID:32808683 (VPS16)
  Authors
Steel D, Zech M, Zhao C, Barwick KES, Burke D, Demailly D, Kumar KR, Zorzi G, Nardocci N, Kaiyrzhanov R, Wagner M, Iuso A, Berutti R, Skorvanek M, Necpal J, Davis R, Wiethoff S, Mankad K, Sudhakar S, Ferrini A, Sharma S, Kamsteeg EJ, Tijssen MA, Verschuuren C, van Egmond ME, Flowers JM, McEntagart M, Tucci A, Coubes P, Bustos BI, Gonzalez-Latapi P, Tisch S, Darveniza P, Gorman KM, Peall KJ, Botzel K, Koch JC, Kmiec T, Plecko B, Boesch S, Haslinger B, Jech R, Garavaglia B, Wood N, Houlden H, Gissen P, Lubbe SJ, Sue CM, Cif L, Mencacci NE, Anderson G, Kurian MA, Winkelmann J
  Title
Loss-of-Function Variants in HOPS Complex Genes VPS16 and VPS41 Cause Early Onset Dystonia Associated with Lysosomal Abnormalities.
  Journal
Ann Neurol 88:867-877 (2020)
DOI:10.1002/ana.25879
Reference
PMID:34596301 (AOPEP)
  Authors
Zech M, Kumar KR, Reining S, Reunert J, Tchan M, Riley LG, Drew AP, Adam RJ, Berutti R, Biskup S, Derive N, Bakhtiari S, Jin SC, Kruer MC, Bardakjian T, Gonzalez-Alegre P, Keller Sarmiento IJ, Mencacci NE, Lubbe SJ, Kurian MA, Clot F, Meneret A, de Sainte Agathe JM, Fung VSC, Vidailhet M, Baumann M, Marquardt T, Winkelmann J, Boesch S
  Title
Biallelic AOPEP Loss-of-Function Variants Cause Progressive Dystonia with Prominent Limb Involvement.
  Journal
Mov Disord (2021)
DOI:10.1002/mds.28804
Reference
PMID:33452836 (VPS11)
  Authors
Monfrini E, Cogiamanian F, Salani S, Straniero L, Fagiolari G, Garbellini M, Carsana E, Borellini L, Biella F, Moggio M, Bresolin N, Corti S, Duga S, Comi GP, Aureli M, Di Fonzo A
  Title
A Novel Homozygous VPS11 Variant May Cause Generalized Dystonia.
  Journal
Ann Neurol 89:834-839 (2021)
DOI:10.1002/ana.26021
Reference
PMID:33236446 (EIF2AK2)
  Authors
Kuipers DJS, Mandemakers W, Lu CS, Olgiati S, Breedveld GJ, Fevga C, Tadic V, Carecchio M, Osterman B, Sagi-Dain L, Wu-Chou YH, Chen CC, Chang HC, Wu SL, Yeh TH, Weng YH, Elia AE, Panteghini C, Marotta N, Pauly MG, Kuhn AA, Volkmann J, Lace B, Meijer IA, Kandaswamy K, Quadri M, Garavaglia B, Lohmann K, Bauer P, Mencacci NE, Lubbe SJ, Klein C, Bertoli-Avella AM, Bonifati V
  Title
EIF2AK2 Missense Variants Associated with Early Onset Generalized Dystonia.
  Journal
Ann Neurol 89:485-497 (2021)
DOI:10.1002/ana.25973
Reference
PMID:32212350 (KCNN2)
  Authors
Balint B, Guerreiro R, Carmona S, Dehghani N, Latorre A, Cordivari C, Bhatia KP, Bras J
  Title
KCNN2 mutation in autosomal-dominant tremulous myoclonus-dystonia.
  Journal
Eur J Neurol 27:1471-1477 (2020)
DOI:10.1111/ene.14228
Reference
PMID:34542157 (SHQ1)
  Authors
Sleiman S, Marshall AE, Dong X, Mhanni A, Alidou-D'Anjou I, Frosk P, Marin SE, Stark Z, Del Bigio MR, McBride A, Sadedin S, Gallacher L, Christodoulou J, Boycott KM, Dragon F, Kernohan KD
  Title
Compound heterozygous variants in SHQ1 are associated with a spectrum of neurological features, including early-onset dystonia.
  Journal
Hum Mol Genet 31:614-624 (2022)
DOI:10.1093/hmg/ddab247

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