title: THAP1/DYT6 sequence variants in non-DYT1 early-onset primary dystonia in China and their effects on RNA expression.
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.
authors.affiliation: Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1# Shuaifuyuan, Wangfujing Street, Beijing, 100075, People's Republic of China.
authors.forename: Fu Bo
authors.initials: FB
authors.lastname: Cheng
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Ozelius
authors.forename: Xin Hua
authors.initials: XH
authors.lastname: Wan
authors.forename: Jia Chun
authors.initials: JC
authors.lastname: Feng
authors.forename: Ling Yan
authors.initials: LY
authors.lastname: Ma
authors.forename: Ying Mai
authors.initials: YM
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002681:China; D004268:DNA-Binding Proteins / Q000235:genetics*; D020821:Dystonic Disorders / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D012313:RNA / Q000096:biosynthesis* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C474080:THAP1 protein, human; D012313:RNA