Inherited Isolated Dystonia: Clinical Genetics and Gene Function

Neurotherapeutics

Volumn 11, Issue 4, 2014, Pages 807-816

  Dauer, William ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

Dystonia Pathogenesis; DYT1 (TOR1A); DYT25 (GNAL); DYT6 (THAP1); Isolated Inherited Dystonia

Indexed keywords

MEMBRANE PROTEIN; TRANSCRIPTION FACTOR; ZINC FINGER PROTEIN; APOPTOSIS REGULATORY PROTEIN; CHAPERONE; DNA BINDING PROTEIN; GUANINE NUCLEOTIDE BINDING PROTEIN ALPHA SUBUNIT; NUCLEAR PROTEIN; OLFACTORY G PROTEIN SUBUNIT ALPHA OLF; THAP1 PROTEIN, HUMAN; TOR1A PROTEIN, HUMAN;

BLEPHAROSPASM; CLINICAL GENETICS; CYTOLOGY; DEGENERATIVE DISEASE; DYSTONIA; DYT1 GENE; DYT25 GENE; DYT6 GENE; GENE; GENE FUNCTION; GENETIC DISORDER; GENOTYPE PHENOTYPE CORRELATION; HUMAN; INDEL MUTATION; MISSENSE MUTATION; NEUROPATHOLOGY; NEUROTRANSMISSION; NONHUMAN; ONSET AGE; PATHOPHYSIOLOGY; PENETRANCE; REVIEW; SEGMENTAL DYSTONIA; TORTICOLLIS; BRAIN; DYSTONIC DISORDER; GENETICS; METABOLISM; MUTATION; NERVE CELL;

APOPTOSIS REGULATORY PROTEINS; BRAIN; DNA-BINDING PROTEINS; DYSTONIC DISORDERS; GTP-BINDING PROTEIN ALPHA SUBUNITS; HUMANS; MOLECULAR CHAPERONES; MUTATION; NEURONS; NUCLEAR PROTEINS;

EID: 84919719359     PISSN: 19337213     EISSN: 18787479     Source Type: Journal    
DOI: 10.1007/s13311-014-0297-7     Document Type: Review

References (114)

1. Albanese A, Bhatia K, Bressman SB, et al. Phenomenology and classification of dystonia: a consensus update. Mov Disord 2013;28:863–873.
2. Tanabe LM, Kim CE, Alagem N, Dauer WT. Primary dystonia: molecules and mechanisms. Nat Rev Neurol 2009;5:598–609.
3. Xiao J, Uitti RJ, Zhao Y, et al. Mutations in CIZ1 cause adult onset primary cervical dystonia. Ann Neurol 2012;71:458–469.
4. Charlesworth, G, Plagnol, V, Holmstrom, KM, et al. Mutations in Ano3 cause dominant craniocervical dystonia: ion channel implicated in pathogenesis. Am J Hum Genet 2012;91:1041–1050.
5. Klein C. Genetics in dystonia. Parkinsonism Relat Disord 2014;20 Suppl 1:S137–S142.
6. Bressman SB, de Leon D, Brin MF, et al. Idiopathic dystonia among Ashkenazi Jews: evidence for autosomal dominant inheritance. Ann Neurol 1989;26:612–620.
7. Bressman SB, de Leon D, Brin MF, et al. Inheritance of idiopathic torsion dystonia among Ashkenazi Jews. Adv Neurol 1988;50:45–56.
8. Gambarin M, Valente EM, Liberini P, et al. Atypical phenotypes and clinical variability in a large Italian family with DYT1-primary torsion dystonia. Mov Disord 2006;21:1782–1784.
9. Fasano A, Nardocci N, Elia AE, Zorzi G, Bentivoglio AR, Albanese A. Non-DYT1 early-onset primary torsion dystonia: comparison with DYT1 phenotype and review of the literature. Mov Disord 2006;21:1411–1418.
10. Bressman SB, Sabatti C, Raymond D, et al. The DYT1 phenotype and guidelines for diagnostic testing. Neurology. 2000;54:1746–1752.
11. Bressman SB, de Leon D, Kramer PL, et al. Dystonia in Ashkenazi Jews: clinical characterization of a founder mutation. Ann Neurol 1994;36:771–777.
12. Yilmaz U, Yuksel D, Atac FB, Yilmaz D, Verdi H, Senbil N. Atypical phenotypes of DYT1 dystonia in three children. Brain Dev 2013;35:356–359.
13. Ozelius, LJ, Hewett, JW, Page, CE, Bressman, SB, Kramer, PL, Shalish, C, de Leon, D, Brin MF, Raymond D, Corey DP, et al. The early-onset torsion dystonia gene (DYT1) encodes an ATP-binding protein. Nat Genet 1997;17:40–48.
14. Hjermind LE, Werdelin LM, Sorensen SA. Inherited and de novo mutations in sporadic cases of DYT1-dystonia. Eur J Hum Genet 2002;10:213–216.
15. Klein C, Brin MF, de Leon D, et al. De novo mutations (GAG deletion) in the DYT1 gene in two non-Jewish patients with early-onset dystonia. Hum Mol Genet 1998;7:1133–1136.
16. Ikeuchi T, Nomura Y, Segawa M, Ozelius LJ, Shimohata T, Tsuji S. Multiple founder effects in Japanese families with primary torsion dystonia harboring the GAG deletion in the Tor1A (DYT1) gene. Neurogenetics. 2002;4:105–106.
17. Eidelberg D, Moeller JR, Antonini A, et al. Functional brain networks in DYT1 dystonia. Ann Neurol 1998;44(3):303–312.
18. Risch NJ, Bressman SB, Senthil G, Ozelius LJ. Intragenic cis and trans modification of genetic susceptibility in DYT1 torsion dystonia. Am J Hum Genet 2007;80:1188–1193.
19. Bruggemann N, Kock N, Lohmann K, et al. The D216H variant in the DYT1 gene: a susceptibility factor for dystonia in familial cases? Neurology 2009;72:1441–1443.
20. Kock N, Naismith TV, Boston HE, et al. Effects of genetic variations in the dystonia protein torsinA: identification of polymorphism at residue 216 as protein modifier. Hum Mol Genet 2006;15:1355–1364.
21. Almasy L, Bressman S, de Leon D, Risch N. Ethnic variation in the clinical expression of idiopathic torsion dystonia. Mov Disord 1997;12:715–721.
22. Clarimon J, Brancati F, Peckham E, et al. Assessing the role of DRD5 and DYT1 in two different case–control series with primary blepharospasm. Mov Disord 2007;22:162–166.
23. Sibbing D, Asmus F, Konig IR, et al. Candidate gene studies in focal dystonia. Neurology 2003;61:1097–1101.
24. Kamm C, Uflacker N, Asmus F, et al. No evidence for THAP1/DYT6 variants as disease modifiers in DYT1 dystonia. Mov Disord 2011;26:2136–2137.
25. Clarimon J, Asgeirsson H, Singleton A, et al. Torsin A haplotype predisposes to idiopathic dystonia. Ann Neurol 2005;57:765–767.
26. Hague S, Klaffke S, Clarimon J, et al. Lack of association with TorsinA haplotype in German patients with sporadic dystonia. Neurology 2006;66:951–952.
27. Bressman SB, de Leon D, Raymond D, et al. Secondary dystonia and the DYTI gene. Neurology. 1997;48:1571–1577.
28. Friedman JRL, Klein C, Leung J, et al. The GAG deletion of the DYT1 gene is infrequent in musicians with focal dystonia. Neurology 2000;55:1417–1418.
29. Schmidt A, Altenmuller E, Jabusch HC, et al. The GAG deletion in Tor1A (DYT1) is a rare cause of complex musician’s dystonia. Parkinsonism Relat Disord 2012;18:690–691.
30. Almasy L, Bressman SB, Raymond D, et al. Idiopathic torsion dystonia linked to chromosome 8 in two Mennonite families. Ann Neurol. 1997;42:670–673.
31. Saunders-Pullman R, Raymond D, Senthil G, et al. Narrowing the DYT6 dystonia region and evidence for locus heterogeneity in the Amish-Mennonites. Am J Med Genet. 2007;143A:2098–2105.
32. Fuchs T, Gavarini S, Saunders-Pullman R, et al. Mutations in the THAP1 gene are responsible for DYT6 primary torsion dystonia. Nat Genet 2009;41:286–288
33. Paisan-Ruiz C, Ruiz-Martinez J, Ruibal M, et al. Identification of a novel THAP1 mutation at R29 amino-acid residue in sporadic patients with early-onset dystonia. Mov Disord 2009;24:2428–2429.
34. Djarmati A, Schneider SA, Lohmann K, et al. Mutations in THAP1 (DYT6) and generalised dystonia with prominent spasmodic dysphonia: a genetic screening study. Lancet Neurol 2009;8:447–452.
35. Bressman SB, Raymond D, Fuchs T, Heiman GA, Ozelius LJ, Saunders-Pullman R. Mutations in THAP1 (DYT6) in early-onset dystonia: a genetic screening study. Lancet Neurol 2009;8:441–446.
36. Clot F, Grabli D, Burbaud P, Aya, M, et al. Screening of the THAP1 gene in patients with early-onset dystonia: myoclonic jerks are part of the dystonia 6 phenotype. Neurogenetics. 2011;12:87–89
37. Blanchard A, Roubertie A, Simonetta-Moreau M, et al. Singular DYT6 phenotypes in association with new THAP1 frameshift mutations. Mov Disord 2011;26:1775–1777.
38. Houlden H, Schneider SA, Paudel R, et al. THAP1 mutations (DYT6) are an additional cause of early-onset dystonia. Neurology 2010;74:846–850.
39. Schneider SA, Ramirez A, Shafiee K, et al. Homozygous THAP1 mutations as cause of early-onset generalized dystonia. Mov Disord 2011;26:858–861.
40. Xiromerisiou G, Dardiotis E, Tsironi EE, et al. THAP1 mutations in a Greek primary blepharospasm series. Parkinsonism Relat Disord 2013;19:404–405.
41. Ozelius LJ, Bressman SB. THAP1: role in focal dystonia? Neurology. 2010;74:192–193.
42. Xiromerisiou G, Houlden H, Scarmeas N, et al. THAP1 mutations and dystonia phenotypes: genotype phenotype correlations. Mov Disord 2012;27:1290–1294.
43. Zittel S, Moll CK, Bruggemann N, et al. Clinical neuroimaging and electrophysiological assessment of three DYT6 dystonia families. Mov Disord 2010;25:2405–2412
44. Fuchs T, Saunders-Pullman R, Masuho I, et al. Mutations in GNAL cause primary torsion dystonia. Nat Genet. 2012;45:88–92
45. Miao J, Wan XH, Sun Y, Feng JC, Cheng FB. Mutation screening of GNAL gene in patients with primary dystonia from Northeast China. Parkinsonism Relat Disord 2013;19:910–912.
46. Vemula SR, Puschmann A, Xiao J, et al. Role of Galpha(olf) in familial and sporadic adult-onset primary dystonia. Hum Mol Genet 2013;22:2510–2519.
47. Dobricic V, Kresojevic N, Westenberger A, et al. De novo mutation in the GNAL gene causing seemingly sporadic dystonia in a Serbian patient. Mov Disord. 2014 Apr 13 [Epub ahead of print]
48. Saunders-Pullman R, Fuchs T, San Luciano M, et al. Heterogeneity in primary dystonia: Lessons from THAP1, GNAL, and TOR1A in Amish-Mennonites. Mov Disord. 2014;29:812–818
49. Kumar KR, Lohmann K, Masuho I, et al. Mutations in GNAL: a novel cause of craniocervical dystonia. JAMA Neurol 2014;71:490–494
50. Prudente CN, Pardo CA, Xiao J, et al. Neuropathology of cervical dystonia. Exp Neurol 2013;241:95–104.
51. Standaert DG. Update on the pathology of dystonia. Neurobiol Dis 2011;42:148–151.
52. Pappas SS, Leventhal DK, Albin RL, Dauer WT. Mouse models of neurodevelopmental disease of the Basal Ganglia and associated circuits. Curr Top Dev Biol 2014;109:97–169.
53. Hanson PI, Whiteheart SW. AAA + proteins: have engine, will work. Nat Rev Mol Cell Biol 2005;6:519–529.
54. Horwich AL. Chaperoned protein disaggregation—the ClpB ring uses its central channel. Cell 2004;119:579–581.
55. Doyle SM, Wickner S. Hsp104 and ClpB: protein disaggregating machines. Trends Biochem Sci 2009;34:40–48.
56. Littleton JT, Barnard RJ, Titus SA, Slind J, Chapman ER, Ganetzky B. SNARE-complex disassembly by NSF follows synaptic-vesicle fusion. Proc Natl Acad Sci USA 2001;98:12233–12238.
57. Kustedjo K, Bracey MH, Cravatt BF. Torsin A and its torsion dystonia-associated mutant forms are lumenal glycoproteins that exhibit distinct subcellular localizations. J Biol Chem 2000;275:27933–27939.
58. Liu Z, Zolkiewska A, Zolkiewski M. Characterization of human torsinA and its dystonia-associated mutant form. Biochem J 2003;374:117–122.
59. Goodchild RE, Dauer WT. Mislocalization to the nuclear envelope: an effect of the dystonia-causing torsinA mutation. Proc Natl Acad Sci USA 2004;101:847–852.
60. Gonzalez-Alegre P, Paulson HL. Aberrant cellular behavior of mutant torsinA implicates nuclear envelope dysfunction in DYT1 dystonia. J Neurosci 2004;24:2593–2601.
61. Naismith TV, Heuser JE, Breakefield XO, Hanson PI. TorsinA in the nuclear envelope. Proc Natl Acad Sci USA 2004;101(20):7612–7617.
62. Goodchild, RE, Dauer, WT. The AAA+ protein torsinA interacts with a conserved domain present in LAP1 and a novel ER protein. J Cell Biol. 2005;168(6):855–862.
63. Goodchild RE, Kim CE, Dauer WT. Loss of the dystonia-associated protein TorsinA selectively disrupts the neuronal nuclear envelope. Neuron 2005;48:923–932.
64. Kim CE, Perez A, Perkins G, Ellisman MH, Dauer WT. A molecular mechanism underlying the neural-specific defect in torsinA mutant mice. Proc Natl Acad Sci USA 2010;107:9861–9866.
65. Zhao C, Brown RS, Chase AR, Eisele MR, Schlieker C. Regulation of Torsin ATPases by LAP1 and LULL1. Proc Natl Acad Sci USA 2013;110:E1545–E1554.
66. Nery FC, Armata IA, Farley JE, et al. TorsinA participates in endoplasmic reticulum-associated degradation. Nat Commun 2011;2:393.
67. Chen P, Burdette AJ, Porter JC, et al. The early-onset torsion dystonia-associated protein, torsinA, is a homeostatic regulator of endoplasmic reticulum stress response. Hum Mol Genet 2010;19:3502–3515.
68. Torres GE, Sweeney AL, Beaulieu JM, Shashidharan P, Caron MG. Effect of torsinA on membrane proteins reveals a loss of function and a dominant-negative phenotype of the dystonia-associated DeltaE-torsinA mutant. Proc Natl Acad Sci USA 2004;101:15650–15655.
69. Hewett JW, Tannous B, Niland BP, etal. Mutant torsinA interferes with protein processing through the secretory pathway in DYT1 dystonia cells. Proc Natl Acad Sci USA 2007;104:7271–7276.
70. Hewett JW, Nery FC, Niland B, et al. siRNA knock-down of mutant torsinA restores processing through secretory pathway in DYT1 dystonia cells. Hum Mol Genet 2008;17:1436–1445.
71. Liang CC, Tanabe LM, Jou S, Chi F, Dauer WT. TorsinA hypofunction causes abnormal twisting movements and sensorimotor circuit neurodegeneration. J Clin Invest. 2014;124:3080–3092.
72. Gerace L. TorsinA and torsion dystonia: unraveling the architecture of the nuclear envelope. Proc Natl Acad Sci USA 2004;101:8839–8840.
73. Worman, HJ, Gundersen, GG. Here come the SUNs: a nucleocytoskeletal missing link. Trends Cell Biol. 2006;16:67–69.
74. Gundersen GG, Worman HJ. Nuclear positioning. Cell 2013;152:1376–1389.
75. Jungwirth MT, Kumar D, Jeong DY, Goodchild RE. The nuclear envelope localization of DYT1 dystonia torsinA-DeltaE requires the SUN1 LINC complex component. BMC Cell Biol 2011;12:24.
76. Nery FC, Zeng J, Niland BP, et al. TorsinA binds the KASH domain of nesprins and participates in linkage between nuclear envelope and cytoskeleton. J Cell Sci. 2008;121:3476–3486.
77. Wilhelmsen K, Litjens SH, Kuikman I, et al. Nesprin-3, a novel outer nuclear membrane protein, associates with the cytoskeletal linker protein plectin. J Cell Biol 2005;171:799–810.
78. Crisp M, Liu Q, Roux K, et al. Coupling of the nucleus and cytoplasm: role of the LINC complex. J Cell Biol 2006;172:41–53.
79. Maric M, Shao J, Ryan RJ, Wong CS, Gonzalez-Alegre P, Roller RJ. A functional role for TorsinA in herpes simplex virus 1 nuclear egress. J Virol 2011;85:9667–9679.
80. Speese SD, Ashley J, Jokhi V, et al. Nuclear envelope budding enables large ribonucleoprotein particle export during synaptic Wnt signaling. Cell 2012;149:832–846.
81. Jokhi V, Ashley J, Nunnari J, et al. Torsin mediates primary envelopment of large ribonucleoprotein granules at the nuclear envelope. Cell Rep 2013;3:988–995.
82. Hewett J, Gonzalez-Agosti C, Slater D, et al. Mutant torsinA, responsible for early-onset torsion dystonia, forms membrane inclusions in cultured neural cells. Hum Mol Genet. 2000;9:1403–1413.
83. O’Farrell C, Hernandez DG, Evey C, Singleton AB, Cookson MR. Normal localization of deltaF323-Y328 mutant torsinA in transfected human cells. Neurosci Lett 2002;327:75–78.
84. Calakos N, Patel VD, Gottron M, et al. Functional evidence implicating a novel TOR1A mutation in idiopathic, late-onset focal dystonia. J Med Genet 2010;47:646–650.
85. Bragg DC, Camp SM, Kaufman CA, et al. Perinuclear biogenesis of mutant torsin-A inclusions in cultured cells infected with tetracycline-regulated herpes simplex virus type 1 amplicon vectors. Neuroscience 2004;125:651–661.
86. Rostasy K, Augood SJ, Hewett JW, et al. TorsinA protein and neuropathology in early onset generalized dystonia with GAG deletion. Neurobiol Dis 2003;12:11–24.
87. Walker RH, Brin MF, Sandu D, Good PF, Shashidharan P. TorsinA immunoreactivity in brains of patients with DYT1 and non-DYT1 dystonia. Neurology 2002;58:120–124.
88. Parrish ML, Sengstag C, Rine JD, Wright RL. Identification of the sequences in HMG-CoA reductase required for karmellae assembly. Mol Biol Cell 1995;6:1535–1547.
89. Naismith TV, Dalal S, Hanson PI. Interaction of torsinA with its major binding partners is impaired by the dystonia-associated DeltaGAG deletion. J Biol Chem 2009;284:27866–27874.
90. Giles LM, Chen J, Li L, Chin LS. Dystonia-associated mutations cause premature degradation of torsinA protein and cell-type-specific mislocalization to the nuclear envelope. Hum Mol Genet 2008;17:2712–2722.
91. Caldwell GA, Cao S, Sexton EG, Gelwix CC, Bevel JP, Caldwell KA. Suppression of polyglutamine-induced protein aggregation in Caenorhabditis elegans by torsin proteins. Hum Mol Genet 2003;12:307–319.
92. Clouaire T, Roussigne M, Ecochard V, Mathe C, Amalric F, Girard JP. The THAP domain of THAP1 is a large C2CH module with zinc-dependent sequence-specific DNA-binding activity. Proc Natl Acad Sci USA 2005;102:6907–6912.
93. Bessiere D, Lacroix C, Campagne S, et al. Structure-function analysis of the THAP zinc finger of THAP1, a large C2CH DNA-binding module linked to Rb/E2F pathways. J Biol Chem 2008;283:4352–4363.
94. Sengel C, Gavarini S, Sharma N, Ozelius LJ, Bragg DC. Dimerization of the DYT6 dystonia protein, THAP1, requires residues within the coiled-coil domain. J Neurochem 2011;118:1087–1100.
95. Blanchard A, Ea V, Roubertie A, et al. DYT6 dystonia: review of the literature and creation of the UMD Locus-Specific Database (LSDB) for mutations in the THAP1 gene. Hum Mutat 2011;32:1213–1224.
96. Campagne S, Muller I, Milon A, Gervais V. Towards the classification of DYT6 dystonia mutants in the DNA-binding domain of THAP1. Nucleic Acids Res 2012;40:9927–9940.
97. Zhao Y, Xiao J, Gong S, Clara JA, Ledoux MS. Neural expression of the transcription factor THAP1 during development in rat. Neuroscience 2013;231:282–295.
98. Cayrol C, Lacroix C, Mathe C, et al. The THAP-zinc finger protein THAP1 regulates endothelial cell proliferation through modulation of pRB/E2F cell-cycle target genes. Blood 2007;109:584–594.
99. Roussigne M, Cayrol C, Clouaire T, Amalric F, Girard JP. THAP1 is a nuclear proapoptotic factor that links prostate-apoptosis-response-4 (Par-4) to PML nuclear bodies. Oncogene 2003;22:2432–2442.
100. Kaiser FJ, Osmanoric A, Rakovic A, et al. The dystonia gene DYT1 is repressed by the transcription factor THAP1 (DYT6). Ann Neurol 2010;68:554–559.
101. Gavarini S, Cayrol C, Fuchs T, et al. Direct interaction between causative genes of DYT1 and DYT6 primary dystonia. Ann Neurol 2010;68:549–553.
102. Mazars R, Gonzalez-de-Peredo A, Cayrol C, et al. The thap-zinc finger protein thap1 associates with coactivator HCF-1 and O-GLcNAc transferase: A link between DYT6 and DYT3 dystonias. J Biol Chem 2010;285:13364–13371
103. Goodchild RE, Grundmann K, Pisani A. New genetic insights highlight ‘old’ ideas on motor dysfunction in dystonia. Trends Neurosci 2013;36:717–725.
104. Herve D. Identification of a specific assembly of the g protein golf as a critical and regulated module of dopamine and adenosine-activated cAMP pathways in the striatum. Front Neuroanat 2011;5:48.
105. Kull B, Svenningsson P, Fredholm BB. Adenosine A(2A) receptors are colocalized with and activate g(olf) in rat striatum. Mol Pharmacol 2000;58:771–777.
106. Herve D, Le Moine C, Corvol JC, et al. Galpha(olf) levels are regulated by receptor usage and control dopamine and adenosine action in the striatum. J Neurosci 2001;21:4390–4399.
107. Pisani A, Bernardi G, Ding J, Surmeier DJ. Re-emergence of striatal cholinergic interneurons in movement disorders. Trends Neurosci 2007;30:545–553.
108. Belluscio L, Gold GH, Nemes A, Axel R. Mice deficient in G(olf) are anosmic. Neuron. 1998;20:69–81.
109. Corvol JC, Studler JM, Schonn JS, Girault JA, Herve D. Galpha(olf) is necessary for coupling D1 and A2a receptors to adenylyl cyclase in the striatum. J Neurochem. 2001;76:1585–1588.
110. Zhuang X, Belluscio L, Hen R. G(olf)alpha mediates dopamine D1 receptor signaling. J Neurosci 2000;20:RC91.
111. Corvol JC, Valjent E, Pascoli V, et al. Quantitative changes in Galphaolf protein levels, but not D1 receptor, alter specifically acute responses to psychostimulants. Neuropsychopharmacology 2007;32:1109–1121.
112. Cenci MA, Konradi C. Maladaptive striatal plasticity in l-DOPA-induced dyskinesia. Prog Brain Res 2010;183:209–233.
113. Quartarone A, Siebner HR, Rothwell JC. Task-specific hand dystonia: can too much plasticity be bad for you? Trends Neurosci 2006;29:192–199.
114. Edwards MJ, Huang YZ, Mir P, Rothwell JC, Bhatia KP. Abnormalities in motor cortical plasticity differentiate manifesting and nonmanifesting DYT1 carriers. Mov Disord 2006;21:2181–2186.