KEGG DISEASE: Primary dystonia

DISEASE: Primary dystonia

Entry

H00831                      Disease

Name

Primary dystonia

Subgroup

DOPA-responsive dystonia (DRD) [DS:H02557]
Episodic kinesigenic dyskinesia (EKD)
Childhood-onset dystonia with optic atrophy and basal ganglia abnormalities (DYTOABG)

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 in ICD-11 classification [BR:br08403]
08 Diseases of the nervous system
  Movement disorders
   8A02  Dystonic disorders
    H00831  Primary dystonia
Pathway-based classification of diseases [BR:br08402]
Cellular process
  nt06515  Regulation of kinetochore-microtubule interactions
   H00831  Primary dystonia
  nt06532  Autophagy
   H00831  Primary dystonia
  nt06535  Efferocytosis
   H00831  Primary dystonia
  nt06539  Cytoskeleton in muscle cells
   H00831  Primary dystonia
  nt06541  Cytoskeleton in neurons
   H00831  Primary dystonia
  nt06548  Integrin signaling
   H00831  Primary dystonia

Pathway

hsa04140

Autophagy - animal

hsa04820

Cytoskeleton in muscle cells

hsa04518

Integrin signaling

Network

nt06515 Regulation of kinetochore-microtubule interactions
nt06532 Autophagy
nt06535 Efferocytosis
nt06539 Cytoskeleton in muscle cells
nt06541 Cytoskeleton in neurons
nt06548 Integrin signaling

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) SLC2A1 [HSA:6513] [KO:K07299]
(DYT10/EKD1) PRRT2 [HSA:112476] [KO:K23897]
(DYT11) SGCE [HSA:8910] [KO:K27061]
(DYT12) ATP1A3 [HSA:478] [KO:K01539]
(DYT16) PRKRA [HSA:8575] [KO:K24540]
(DYT22JO/AO) TSPOAP1 [HSA:9256] [KO:K19922]
(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/DYTOABG) 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]
(DYT36/EKD3) TMEM151A [HSA:256472] [KO:K28463]
(DYT37) NUP54 [HSA:53371] [KO:K14308]

Other DBs

ICD-11:

8A02.0

MeSH:

D020821

Reference

PMID:22030388

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

PMID:20425035

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

PMID:19578124

Authors

Muller U

Title

The monogenic primary dystonias.

Journal

Brain 132:2005-25 (2009)
DOI:10.1093/brain/awp172

Reference

PMID:21907099

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 (DYT1)

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 (DYT2)

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 (DYT3)

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 (DYT4)

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 (DYT5)

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 (DYT6)

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 (DYT8)

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 (DYT9)

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 (DYT10, EKD1)

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 (DYT11)

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 (DYT12)

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 (DYT16)

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:33539324 (DYT22JO/DYT22AO)

Authors

Mencacci NE, Brockmann MM, Dai J, Pajusalu S, Atasu B, Campos J, Pino G, Gonzalez-Latapi P, Patzke C, Schwake M, Tucci A, Pittman A, Simon-Sanchez J, Carvill GL, Balint B, Wiethoff S, Warner TT, Papandreou A, Soo A, Rein R, Kadastik-Eerme L, Puusepp S, Reinson K, Tomberg T, Hanagasi H, Gasser T, Bhatia KP, Kurian MA, Lohmann E, Ounap K, Rosenmund C, Sudhof TC, Wood NW, Krainc D, Acuna C

Title

Biallelic variants in TSPOAP1, encoding the active-zone protein RIMBP1, cause autosomal recessive dystonia.

Journal

J Clin Invest 131:140625 (2021)
DOI:10.1172/JCI140625

Reference

PMID:23200863 (DYT24)

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 (DYT25)

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 (DYT26)

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 (DYT27)

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 (DYT28)

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 (DYT29)

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 (DYT30)

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 (DYT31)

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 37:137-147 (2022)
DOI:10.1002/mds.28804

Reference

PMID:33452836 (DYT32)

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 (DYT33)

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 (DYT34)

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 (DYT35)

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

Reference

PMID:36856871 (DYT36, EKD3)

Authors

Huang HL, Zhang QX, Huang F, Long XY, Song Z, Xiao B, Li GL, Ma CY, Liu D

Title

TMEM151A variants associated with paroxysmal kinesigenic dyskinesia.

Journal

Hum Genet 142:1017-1028 (2023)
DOI:10.1007/s00439-023-02535-3

Reference

PMID:36333996 (DYT37)

Authors

Harrer P, Schalk A, Shimura M, Baer S, Calmels N, Spitz MA, Warde MA, Schaefer E, Kittke VMS, Dincer Y, Wagner M, Dzinovic I, Berutti R, Sato T, Shirakawa T, Okazaki Y, Murayama K, Oexle K, Prokisch H, Mall V, Melcak I, Winkelmann J, Zech M

Title

Recessive NUP54 Variants Underlie Early-Onset Dystonia with Striatal Lesions.

Journal

Ann Neurol 93:330-335 (2023)
DOI:10.1002/ana.26544

LinkDB

» Japanese version

DISEASE: Bethlem myopathy

Entry

H01340                      Disease

Name

Bethlem myopathy

Subgroup

Bethlem myopathy 2 [DS:H02247]

Supergrp

Collagen VI myopathy [DS:H01341]
Congenital muscular dystrophies (CMD/MDC) [DS:H00590]

Description

Bethlem myopathy is one of the collagen VI myopathies, caused by mutation of COL6A. Bethlem myopathy is usually inherited in an autosomal dominant manner, but a rare autosomal recessive inheritance has recently been reported. This disease is characterized by a combination of proximal muscle weakness and contractures of finger, elbow, and ankle joints.