Dystonia is a syndrome which is characterized by sustained muscle contractions, producing twisting, repetitive, and patterned movements, or abnormal postures. According to genetic basis, dystonia is classified into 13...Dystonia is a syndrome which is characterized by sustained muscle contractions, producing twisting, repetitive, and patterned movements, or abnormal postures. According to genetic basis, dystonia is classified into 13 subtypes. We mainly discussed two subtypes, DYT1 and DYT5, in this review. Early-onset primary dystonia is caused by the mutation of DYT1 gene, which leads to TORSINA abnormal. GTP cyclohydrolase 1 (GTPCH1)-deficient DRD(DYT5) is caused by the mutations of GCH1 gene. By genetic testing, we can confirm clinical diagnosis of each subtype and develop prenatal diagnosis for it.展开更多
Objective To investigate the frequency of GAG deletion in the DYT1 gene among early onset primary dystonia patients in China.Methods Thirteen patients with early onset primary torsion dystonia were screened for mutati...Objective To investigate the frequency of GAG deletion in the DYT1 gene among early onset primary dystonia patients in China.Methods Thirteen patients with early onset primary torsion dystonia were screened for mutation in exon 5 of the DYT1 gene using denaturing high-performance liquid chromatography(DHPLC)and DNA sequencing,and the results were confirmed with polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).Results The GAG deletion mutation which results in Glu302del in exon 5 of the DYT1 gene was found in 5 patients.The detecting results were consistent between with DHPLC and PCR-RFLP.We did not find any other mutations in the DYT1 gene.Conclusions The GAG deletion in the DYT1 gene is common amongst early onset primary torsion dystonia patients in China.The frequency of DYT1 mutation is not significantly different between European and Asian patients with early onset primary dystonia.展开更多
Dystonia is a common movement disorder characterized by sustained or intermittent muscle contractions causing abnormal movements and/or postures(Keller Sarmiento and Mencacci,2021).The dystonic syndromes are classifie...Dystonia is a common movement disorder characterized by sustained or intermittent muscle contractions causing abnormal movements and/or postures(Keller Sarmiento and Mencacci,2021).The dystonic syndromes are classified as primary dystonia(dystonia is the only motor feature without tremor) and the secondary dystonia(dystonia is combined with other movement disorders,such as Parkinsonism).展开更多
To determine whether reduced striatal D2 receptor binding reported in patients with idiopathic torsion dystonia is associated with the genotype, the authors used PET and [11C]- raclopride to assess non- manifesting ca...To determine whether reduced striatal D2 receptor binding reported in patients with idiopathic torsion dystonia is associated with the genotype, the authors used PET and [11C]- raclopride to assess non- manifesting carriers of the DYT1 mutation. D2 receptor binding was reduced by approximately 15% in caudate and putamen (p < 0.005). These results suggest that striatal D2 binding reductions are a trait feature of the DYT1 genotype.展开更多
Mutation of the DYT1 gene has been reported to cause early-onset primary torsion dystonia (DYT1).Due to DYT1 gene mutation,defective wild torsinA and the accumulation of mutant torsinA (GAG-deleted DYT1 gene encoded t...Mutation of the DYT1 gene has been reported to cause early-onset primary torsion dystonia (DYT1).Due to DYT1 gene mutation,defective wild torsinA and the accumulation of mutant torsinA (GAG-deleted DYT1 gene encoded the mutant torsinA,torsinA?E) play an important role in DYT1 pathogenesis.Intracellular inclusion bodies are formed,and dopamine transport and release are disturbed by interfering functions of endoplasmic reticulum,nuclear membrane,and cytoskeleton of neural cells,resulting in DYT1 onset.Small interfering RNA could serve as a potential therapy for DYT1.However,the exact function of wild torsinA and the pathological effects of torsinA?E require further studies.展开更多
Primary torsion dystonia （PTD） is a clinically and genetically heterogeneous movement disorder. At least thirteen different types of dystonia can be distinguished on a genetic basis.1 The DYT1 gene was first mapped ...Primary torsion dystonia （PTD） is a clinically and genetically heterogeneous movement disorder. At least thirteen different types of dystonia can be distinguished on a genetic basis.1 The DYT1 gene was first mapped by Ozelius et al in 1989.2 （Kramer et） al3 linked the same locus to PTD in 12 Ashkenazi Jewish families in 1990. Most patients with early-onset generalized PTD were caused by the same three base pair （GAG） deletion in the DYT1 gene on chromosome 9q34.1,4,5 The product of the gene is a protein called torsinA.5 （Although the） function of this protein is as yet uncertain, it is widely distributed throughout the brain with high levels in the substantia nigra compacta dopamine neurones.展开更多
The Arabidopsis b HLH010/089/091(basic helix-loop-helix)genes are functionally redundant and are required for both anther development and normal expression of DYT1-activated anther-related genes.These three genes are ...The Arabidopsis b HLH010/089/091(basic helix-loop-helix)genes are functionally redundant and are required for both anther development and normal expression of DYT1-activated anther-related genes.These three genes are conserved in Brassicaceae,suggesting that each of them is under selection pressure;however,little is known about the possible functional differences among these b HLH genes and between the b HLH and DYT1 genes.Here,we compared novel anther transcriptomic data sets from b HLH010/089/091 single and double mutants,with an anther transcriptomic data set from the wild type(WT)and a previously obtained anther transcriptomic data set from the bhlh010 bhlh089 bhlh091 triple mutant.The results revealed molecular phenotypes that support the functional redundancy and divergence of b HLH010,b HLH089,and b HLH091,as well as the functional overlap and difference between them and DYT1.DNA-binding analyses revealed that DYT1 and b HLH089 specifically recognize the TCATGTGC box to activate the expression of target genes,including ATA20,EXL4,and MEE48.In addition,among genes whose expression was affected in the bhlh010 bhlh089 double and bhlh010 bhlh089 bhlh091 triple mutants,genes that are involved in the stress response and cell signaling were enriched,which included256 genes whose expression was preferentially induced by heat during early flower development.Moreover,the bhlh double mutants exhibited defective pollen development when the plants were grown under elevated temperature,suggesting that b HLH genes are important for anther gene expression under such conditions.These results are consistent with the observation that the heat-induced expression of several genes is less in the bhlh mutants than that in the WT.Therefore,our results provide important insights into the molecular mechanism underlying the activation of direct targets by DYT1-b HLH089 heterodimers and demonstrate the protective roles of b HLH010/089/091 in maintaining fertility upon heat stress.展开更多
In anther development, tapetal cells take part in complex processes, including endomitosis and apoptosis (programmed cell death). The tapetum provides many of the proteins, lipids, polysaccharides and other molecules ...In anther development, tapetal cells take part in complex processes, including endomitosis and apoptosis (programmed cell death). The tapetum provides many of the proteins, lipids, polysaccharides and other molecules necessary for pollen development. Several transcription factors, including DYT1, TDF1, AMS, MS188 and MS1, have been reported to be essential for tapetum development and function in Arabidopsis thaliana. Here, we present a detailed cytological analysis of knockout mutants for these genes, along with an in situ RNA hybridization experiment and double mutant analysis showing that these transcription factors form a genetic pathway in tapetum development. DYT1, TDF1 and AMS function in early tapetum development, while MS188 and MS1 are important for late tapetum development. The genetic pathway revealed in this work facilitates further investigation of the function and molecular mechanisms of tapetum development in Arabidopsis.展开更多
文摘Dystonia is a syndrome which is characterized by sustained muscle contractions, producing twisting, repetitive, and patterned movements, or abnormal postures. According to genetic basis, dystonia is classified into 13 subtypes. We mainly discussed two subtypes, DYT1 and DYT5, in this review. Early-onset primary dystonia is caused by the mutation of DYT1 gene, which leads to TORSINA abnormal. GTP cyclohydrolase 1 (GTPCH1)-deficient DRD(DYT5) is caused by the mutations of GCH1 gene. By genetic testing, we can confirm clinical diagnosis of each subtype and develop prenatal diagnosis for it.
基金The Science and Technology Commission of Shanghai Municipality(08PJ1405500)The National Natural Science Foundation of China(30870225)The Shanghai Municipality Education Commission 2009 Innovation Project of Science and Technology
基金Supported by grants from Ministry of Sciences and Technology of China(2006CB500701,2002BA711A10)National Natural Science Foundation of China(30430280)+1 种基金Beijing Municipal Commission on Sciences and Technology(H020220020610,7031002)Beijing Bureau of Health(2003-2029)
文摘Objective To investigate the frequency of GAG deletion in the DYT1 gene among early onset primary dystonia patients in China.Methods Thirteen patients with early onset primary torsion dystonia were screened for mutation in exon 5 of the DYT1 gene using denaturing high-performance liquid chromatography(DHPLC)and DNA sequencing,and the results were confirmed with polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).Results The GAG deletion mutation which results in Glu302del in exon 5 of the DYT1 gene was found in 5 patients.The detecting results were consistent between with DHPLC and PCR-RFLP.We did not find any other mutations in the DYT1 gene.Conclusions The GAG deletion in the DYT1 gene is common amongst early onset primary torsion dystonia patients in China.The frequency of DYT1 mutation is not significantly different between European and Asian patients with early onset primary dystonia.
基金supported by National Institute of Neurological Diseases and Stroke,No.NIH/NINDS NS112910 (to BD)Department of Defense (DoD) Peer Reviewed Medical Research Program (PRMRP) Discovery Award,No.W81XWH2010186 (to BD)。
文摘Dystonia is a common movement disorder characterized by sustained or intermittent muscle contractions causing abnormal movements and/or postures(Keller Sarmiento and Mencacci,2021).The dystonic syndromes are classified as primary dystonia(dystonia is the only motor feature without tremor) and the secondary dystonia(dystonia is combined with other movement disorders,such as Parkinsonism).
文摘To determine whether reduced striatal D2 receptor binding reported in patients with idiopathic torsion dystonia is associated with the genotype, the authors used PET and [11C]- raclopride to assess non- manifesting carriers of the DYT1 mutation. D2 receptor binding was reduced by approximately 15% in caudate and putamen (p < 0.005). These results suggest that striatal D2 binding reductions are a trait feature of the DYT1 genotype.
基金the National Natural Science Foundation of China,No.30400144
文摘Mutation of the DYT1 gene has been reported to cause early-onset primary torsion dystonia (DYT1).Due to DYT1 gene mutation,defective wild torsinA and the accumulation of mutant torsinA (GAG-deleted DYT1 gene encoded the mutant torsinA,torsinA?E) play an important role in DYT1 pathogenesis.Intracellular inclusion bodies are formed,and dopamine transport and release are disturbed by interfering functions of endoplasmic reticulum,nuclear membrane,and cytoskeleton of neural cells,resulting in DYT1 onset.Small interfering RNA could serve as a potential therapy for DYT1.However,the exact function of wild torsinA and the pathological effects of torsinA?E require further studies.
文摘Primary torsion dystonia （PTD） is a clinically and genetically heterogeneous movement disorder. At least thirteen different types of dystonia can be distinguished on a genetic basis.1 The DYT1 gene was first mapped by Ozelius et al in 1989.2 （Kramer et） al3 linked the same locus to PTD in 12 Ashkenazi Jewish families in 1990. Most patients with early-onset generalized PTD were caused by the same three base pair （GAG） deletion in the DYT1 gene on chromosome 9q34.1,4,5 The product of the gene is a protein called torsinA.5 （Although the） function of this protein is as yet uncertain, it is widely distributed throughout the brain with high levels in the substantia nigra compacta dopamine neurones.
基金financially supported by grants from the National Natural Science Foundation of China(31822005,31670316,and 31870294)
文摘The Arabidopsis b HLH010/089/091(basic helix-loop-helix)genes are functionally redundant and are required for both anther development and normal expression of DYT1-activated anther-related genes.These three genes are conserved in Brassicaceae,suggesting that each of them is under selection pressure;however,little is known about the possible functional differences among these b HLH genes and between the b HLH and DYT1 genes.Here,we compared novel anther transcriptomic data sets from b HLH010/089/091 single and double mutants,with an anther transcriptomic data set from the wild type(WT)and a previously obtained anther transcriptomic data set from the bhlh010 bhlh089 bhlh091 triple mutant.The results revealed molecular phenotypes that support the functional redundancy and divergence of b HLH010,b HLH089,and b HLH091,as well as the functional overlap and difference between them and DYT1.DNA-binding analyses revealed that DYT1 and b HLH089 specifically recognize the TCATGTGC box to activate the expression of target genes,including ATA20,EXL4,and MEE48.In addition,among genes whose expression was affected in the bhlh010 bhlh089 double and bhlh010 bhlh089 bhlh091 triple mutants,genes that are involved in the stress response and cell signaling were enriched,which included256 genes whose expression was preferentially induced by heat during early flower development.Moreover,the bhlh double mutants exhibited defective pollen development when the plants were grown under elevated temperature,suggesting that b HLH genes are important for anther gene expression under such conditions.These results are consistent with the observation that the heat-induced expression of several genes is less in the bhlh mutants than that in the WT.Therefore,our results provide important insights into the molecular mechanism underlying the activation of direct targets by DYT1-b HLH089 heterodimers and demonstrate the protective roles of b HLH010/089/091 in maintaining fertility upon heat stress.
基金supported by grants from the National Natural Science Foundation of China (30925007)Shanghai(11ZR1425800)the State Key Basic Research and Development Program of China (2007CB947600)
文摘In anther development, tapetal cells take part in complex processes, including endomitosis and apoptosis (programmed cell death). The tapetum provides many of the proteins, lipids, polysaccharides and other molecules necessary for pollen development. Several transcription factors, including DYT1, TDF1, AMS, MS188 and MS1, have been reported to be essential for tapetum development and function in Arabidopsis thaliana. Here, we present a detailed cytological analysis of knockout mutants for these genes, along with an in situ RNA hybridization experiment and double mutant analysis showing that these transcription factors form a genetic pathway in tapetum development. DYT1, TDF1 and AMS function in early tapetum development, while MS188 and MS1 are important for late tapetum development. The genetic pathway revealed in this work facilitates further investigation of the function and molecular mechanisms of tapetum development in Arabidopsis.
