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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&#95;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.

Background: Schizophrenia is a common yet severe psychiatric condition characterized by complex genetic mechanism and diverse clinical presentations. Our previous study indicated that the combined effect of two intronic single nucleotide polymorphisms (SNPs), which are located in the catechol-O-methyltransferase (COMT) and aldehyde dehydrogenase 3B1 (ALDH3B1) genes, respectively, conferred genetic risk to paranoid schizophrenia., Methods: To further explore the precise mechanism of the COMT and ALDH3B1 interaction involved in the pathophysiology of schizophrenia, we scanned all possible functional SNPs within these two genes by polymerase chain reaction (PCR)-based genotyping analysis in 540 paranoid schizophrenic patients and 660 control subjects from a Han Chinese population. We also determined the effects of schizophrenia-associated SNPs on the development of psychotic symptoms, P300 event-related potential components induced by an auditory odd-ball task, and gene expression examined by quantitative real-time PCR analysis., Results: The major findings of this study were that, among the individuals carrying the rs3751082 A allele in the ALDH3B1 gene, the rs4633 T allele in the COMT gene was associated with susceptibility to paranoid schizophrenia (p = .004), development of hallucination (p = 5.141 E-5), delay of P300 latency in both patients (p = .006) and control subjects (p = .02), and increased expression of the COMT gene in control subjects (p = .002). However, the rs4633 T allele did not show any association in the rs3751082 G/G genotype carriers., Conclusions: These findings provided convincing evidence that epistasis between the COMT and ALDH3B1 genes plays an important role in the pathogenesis of schizophrenia.