Journal of Neurology

, Volume 259, Issue 2, pp 342–347

THAP1/DYT6 sequence variants in non-DYT1 early-onset primary dystonia in China and their effects on RNA expression

  • Fu Bo Cheng
  • Laurie J. Ozelius
  • Xin Hua Wan
  • Jia Chun Feng
  • Ling Yan Ma
  • Ying Mai Yang
  • Lin Wang
Original Communication

DOI: 10.1007/s00415-011-6196-5

Cite this article as:
Cheng, F.B., Ozelius, L.J., Wan, X.H. et al. J Neurol (2012) 259: 342. doi:10.1007/s00415-011-6196-5

Abstract

Mutations in the THAP1 gene were recently identified as the cause of DYT6 primary dystonia. More than 40 mutations in this gene have been described in different populations. However, no previous report has identified sequence variations that affect the transcript process of the THAP1 gene. In addition, the mutation frequency in Chinese early-onset primary dystonia has not been well characterized. One hundred and two unrelated patients with non-DYT1 early-onset primary dystonia (age at onset <26 years), family members of participants with mutations, and 200 neurologically normal controls were screened for THAP1 gene mutations. The effects of the identified mutations on RNA expression were analyzed using semi-quantitative real-time PCR. Seven sequence variants (c.63_66del TTTC, c.161G>T, c.224A>T, c.267G>A, c.339T>C, c.449A>C, and c.539T>C) were identified in this group of patients (6.9%). In this cohort, 15 subjects (seven unrelated patients and eight family members) were detected to have THAP1 sequence variants. Among these 15 subjects, 11 were manifested (penetrance of DYT6 was 73.3%) and seven presented with craniocervical involvement (63.6%). However, one patient manifested paroxysmal headshake, and one presented with essential hand tremor. Semi-quantitative real-time PCR indicated that a novel silent mutation (c.267G>A) decreased the expression of THAP1 in human lymphocytes. Our findings indicated that THAP1 sequence variants are not common in non-DYT1 early-onset primary dystonia in China and that the clinical manifestation may vary. One silent mutation (c.267G>A) was shown to affect THAP1 expression.

Keywords

Non-DYT1 early-onset primary dystonia THAP1/DYT6 variants Silent mutation Exon skipping RNA expression 

Supplementary material

415_2011_6196_MOESM1_ESM.doc (28 kb)
Supplementary material 1 (DOC 27 kb)

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Fu Bo Cheng
    • 1
    • 2
  • Laurie J. Ozelius
    • 3
  • Xin Hua Wan
    • 1
  • Jia Chun Feng
    • 2
  • Ling Yan Ma
    • 1
  • Ying Mai Yang
    • 1
  • Lin Wang
    • 1
  1. 1.Department of Neurology, Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijingPeople’s Republic of China
  2. 2.Department of NeurologyThe First Affiliated Hospital of Jilin UniversityJilinPeople’s Republic of China
  3. 3.Department of Genetics and Genomic Sciences and NeurologyMount Sinai School of MedicineNew YorkUSA

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