DYT6 form of idiopathic dystonia

Cover Page


Cite item

Full Text

Abstract

DYT6 is a recently described autosomal dominant form of primary dystonia with early onset of symptoms caused by mutations in THAP1 gene in chromosome 8. The incidence of this form in various populations is extremely variable and ranges from 1% to 25%. Knowledge of the molecular defect underlying the disease largely determines its prognosis and treatment approaches. The article presents the first in the Russian population case of DYT6 dystonia, which was confirmed by detection of c.424A> G (p.T142A) mutation in THAP1 gene. Clinical presentation included acute manifestation of symptoms at the age of 27 years with the development of left-directed latero-retrocollis. The incidence of this form of dystonia in our population of dystonic syndromes was 0.7%. We emphasize phenotypic polymorphism of DYT6 dystonia and the role of genetic testing in its diagnosis.

About the authors

M. Yu. Krasnov

Research Center of Neurology

Email: merritt.kraut@gmail.com
Россия, Moscow

Sofiya L. Timerbaeva

Research Center of Neurology

Email: merritt.kraut@gmail.com
Россия, Moscow

Natal’ya Yu. Abramycheva

Research Center of Neurology

Email: merritt.kraut@gmail.com
Россия, Moscow

M. S. Stepanova

Research Center of Neurology

Email: merritt.kraut@gmail.com
Россия, Moscow

Yuliya A. Shpilyukova

Research Center of Neurology

Email: merritt.kraut@gmail.com
ORCID iD: 0000-0001-7214-583X

Cand. Sci. (Med.), junior researcher, neurologist, 5th Neurology department

Россия, Moscow

Margarita V. Ershova

Research Center of Neurology

Author for correspondence.
Email: merritt.kraut@gmail.com
Россия, Moscow

References

  1. Иллариошкин С.Н. Паркинсонизм с ранним началом. Нервные болезни. 2006; 3: 14–20.
  2. Иллариошкин С.Н., Маркова Е.Д., Миклина Н.И., Иванова-Смоленская И.А. Молекулярная генетика наследственных дистонических синдромов. Журн. неврол. и психиатрии им. С.С. Корсакова. 2000; 8: 60–66.
  3. Краснов М.Ю., Тимербаева С.Л., Иллариошкин С.Н. Генетика наследственных форм дистонии. Анн. клинич. и эксперим. неврол. 2013; 2: 55–62.
  4. Тимербаева С.Л. Фокальные и сегментарные формы первичной дистонии: клинические, патофизиологические и молекулярно-генетические аспекты. Дис. … докт. мед. наук. М., 2012.
  5. Экстрапирамидные расстройства. Руководство по диагностике и лечению (под ред. В.Н. Штока, И.А. Ивановой-Смоленской,О.С. Левина). М.: МЕДпресс-информ, 2002.
  6. Albanese A., Asmus F., Bhatia K.P. et al. EFNS guidelines on diagnosis and treatment of primary dystonias. Eur. J. Neurol. 2011; 18: 5–18.
  7. Albanese A., Bhatia K., Bressman S.B. et al. Phenomenology and classification of dystonia: a consensus update. Mov. Disord. 2013; 28:863–873.
  8. 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.
  9. Bressman S.B. Genetics of dystonia: an overview. Parkinsonism Relat. Disord. 2007; 13: 347–355.
  10. Bressman S.B., Raymond D., Fuchs T. THAP1 (DYT6) mutations in early-onset primary dystonia. Lancet Neurol. 2009; 8: 441–446.
  11. Djarmati A., Schneider S.A., Lohmann K. et al. Mutations in THAP1 (DYT6) and generalized dystonia with prominent spasmodic dysphonia: a genetic screening study. Lancet Neurol. 2009; 8: 447–452.
  12. Dobričić V.S., Kresojević N.D., Svetel M.V. et al. Mutation screening of the DYT6/THAP1 gene in Serbian patients with primary dystonia.J. Neurol. 2013; 260: 1037–1042.
  13. Epidemiological Study of Dystonia in Europe (ESDE) Collaborative Group. A prevalence study of primary dystonia in eight European countries. J. Neurol. 2000; 247: 787–792.
  14. Golanska E., Gajos A., Sieruta M. et al. Screening for THAP1 mutations in Polish patients with dystonia shows known and novel substitutions. PLoS One. 2015; 10 (6): e0129656.
  15. Groen J.L., Ritz K., Contarino M.F. et al. DYT6 dystonia: mutation screening, phenotype, and response to deep brain stimulation. Mov.Disord. 2010; 25: 2420–2427.
  16. Houlden H., Schneider S.A., Paudel R. et al. THAP1 mutations (DYT6) are an additional cause of early-onset dystonia. Neurology. 2010; 74: 846–850.
  17. Illarioshkin S.N., Ivanova-Smolenskaya I.A., Markova E.D. et al. Molecular genetic analysis of essential tremor. Russian Journal of Genetics. 2002; 12: 1447–1451.
  18. Illarioshkin S.N., Markova E.D., Slominsky P.A. et al. The GTP cyclohydrolase I gene in Russian families with dopa responsive dystonia. Arch. Neurol. 1998; 55: 789–792.
  19. Illarioshkin S.N., Tanaka H., Tsuji S. et al. Refined genetic location of the chromosome 2p-linked progressive muscular dystrophy gene.Genomics. 1997; 42 (2): 345–348.
  20. Illarioshkin S.N., Zagorovskaya T.B., Bagyeva G.Kh. et al. A common leucine-rich repeat kinase 2 gene mutation in familial and sporadic Parkinson’s disease in Russia. Eur. J. Neurol. 2007; 14: 413–417.
  21. Jinnah H.A., Hess E.J. A new twist on the anatomy of dystonia: the basal ganglia and the cerebellum? Neurology. 2006; 67: 1740–1741.
  22. Kaiser F.J., Osmanoric A., Rakovic A. et al. The dystonia gene DYT1 is repressed by the transcription factor THAP1 (DYT6). Ann. Neurol. 2010; 68: 554–559.
  23. Muller U. The monogenic primary dystonias. Brain. 2009; 132: 2005–2025.
  24. Ozelius L.J., Bressman S.B. THAP1: role in focal dystonia? Neurology. 2010; 74: 192–193.
  25. Ozelius L.J., Lubarr N., Bressman S.B. Milestones in dystonia. Mov Disord. 2011; 26: 1106–1126.
  26. Paudel R., Li A., Hardy J. et al. DYT6 dystonia: A neuropathological study. Neurodegener. Dis. 2015; Nov 27. [Epub ahead of print]
  27. Sengel C., Gavarini S., Sharma N. et al. Dimerization of the DYT6 dystonia protein, THAP1, requires residues within the coiled-coil domain. J. Neurochem. 2011; 118: 1087–1100.
  28. Slominsky P.A., Markova E.D., Shadrina M.I. et al. A common 3-bp deletion in the DYT1 gene in Russian families with early-onset torsion dystonia. Human Mutation. 1999; 14 (3): 269.
  29. Steeves T.D, Day L., Dykeman J. et al. The prevalence of primary dystonia: A systematic review and meta-analysis. Mov. Disord. 2012; 27: 1789–1796.
  30. Xiromerisiou G., Houlden H., Scarmeas N. et al. THAP1 mutations and dystonia phenotypes: genotype-phenotype correlations. Mov. Disord. 2012; 27: 1290–1294.
  31. Zittel S., Moll C.K., Bruggemann N. et al. Clinical neuroimaging and electrophysiological assessment of three DYT6 dystonia families. Mov. Disord. 2010; 25: 2405–2412.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2016 Krasnov M.Y., Timerbaeva S.L., Abramycheva N.Y., Stepanova M.S., Shpilyukova Y.A., Ershova M.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77-83204 от 12.05.2022.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies