Genetic classification and molecular mechanisms of primary dystonia

Xueping Chen; Huifang Shang; Zuming Luo

摘要：BACKGROUND: Primary dystonia is a heterogeneous disease, with a complex genetic basis. In previous studies, primary dystonia was classified according to age of onset, involved regions, and other clinical characteristics. With the development of molecular genetics, new virulence genes and sites have been discovered. Therefore, there is a gradual understanding of the various forms of dystonia, based on new viewpoints. There are 15 subtypes of dystonia, based on the molecular level, i.e., DYT1 to DYT15. OBJECTIVE: To analyze the genetic development of dystonia in detail, and to further investigate molecular mechanisms of dystonia. RETRIEVAL STRATEGY: A computer-based online search was conducted in PubMed for English language publications containing the keywords "dystonia and genetic" from January 1980 to March 2007. There were 105 articles in total. Inclusion criteria: ① the contents of the articles should closely address genetic classification and molecular mechanisms of primary dystonia; ② the articles published in recent years or in high-impact journals took preference. Exclusion criteria: duplicated articles. LITERATURE EVALUATION: The selected articles were on genetic classification and molecular genetics mechanism of primary dystonia. Of those, 27 were basic or clinical studies. DATA SYNTHESIS: ① Dystonia is a heterogeneous disease, with a complex genetic basis. According to the classification of the Human Genome Organization, there are 15 dystonia subtypes, based on genetics, i.e., DYT1-DYT15,including primary dystonia, dystonia plus syndrome, degeneration plus dystonia, and paroxysmal dyskinesia plus dystonia. ② To date, the chromosomes of 13 subtypes have been localized; however, DYT2 and DYT4 remain unclear. Six subtypes have been located within virulence genes. Specifically, torsinA gene expression results in the DYT1 genotype; autosomal dominant GTP cyclohydrolase I gene expression and recessive tyrosine hydroxylase expression result in the DYT5 genotype, respectively; the epsilon-sarcoglycan gene is involved in DYT11; Na+/K+-ATP enzyme α3 chain gene in DYT12; TATA-conjugated protein-associated factor 1 gene in DYT3; and myofibril regulatory factor gene in DYT8. ③ Different types of dystonia exhibit various clinical characteristics and specific clinical manifestations. ④ Many elements regarding the molecular mechanism of dystonia have been determined. However, many components remain poorly understood. For example, detailed pathogenesis remains unclear. Various forms of dystonia exhibit similar problems. Moreover, a single form of dystonia may be a result of two or more different chromosomal mutations. In addition, more studies are needed to fully understand chromosome apposition and virulence genes involved in dystonia. CONCLUSION: The discovery of virulence genes and localizations of newly classified forms of dystonia are beneficial to further understanding the molecular mechanisms of dystonia.