RESUMO
The ubiquitin carboxy-terminal hydrolase L1 gene (UCH-L1) has been implicated in the etiology of Parkinson's disease (PD). In several previous studies, an S18Y (C54A) polymorphism in exon 3 of the UCH-L1 gene has been found to be protective against PD. We performed polymerase chain reaction-restriction fragment length polymorphism analysis for DNA samples from 408 Chinese patients with PD and 398 Chinese healthy controls. For the S18Y variant, there was no significant difference either in the individual allele or genotype frequencies between cases and control subjects. Possession of the S18Y variant did not alter the risk of developing PD (odds ratio: 0.827; 95% confidence interval=0.596-1.147). There was no statistically significant difference in terms of age or sex distribution between the patients and controls (p>0.05). Overall, considering our present results together with those of our previous studies, we now have access to data from more than 1000 patients from different regions of China, supporting the conclusion that the S18Y polymorphism may not have a protective effect against PD in the Chinese population.
Assuntos
Povo Asiático/genética , Predisposição Genética para Doença/genética , Doença de Parkinson/genética , Ubiquitina Tiolesterase/genética , Adolescente , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Criança , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
Mutations in the Parkin, PINK1, and DJ-1 genes can cause autosomal recessive early onset Parkinsonism. We studied three families with the mutations of the Parkin, PINK1 and DJ-1 genes, respectively, with a dopamine transporter ligand [(11)C]-CFT positron emission tomography. A marked bilaterally and dissymmetrically decrement of [(11)C]-CFT uptake was found in all these patients, and putamen as well as caudate nucleus was affected. We also found asymptomatic Parkin and PINK1 heterozygotes showed a mild but significant decrement in [(11)C]-CFT uptake, but this phenomenon was not found in the DJ-1-heterozygotes. Our results suggested the three autosomal recessive forms of early onset are similar to each other on pathophysiological grounds, a sub-clinical disease process in Parkin and PINK1-heterozygotes, but not in DJ-1-heterozygotes.
Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas Oncogênicas/genética , Transtornos Parkinsonianos/diagnóstico por imagem , Transtornos Parkinsonianos/genética , Proteínas Quinases/genética , Ubiquitina-Proteína Ligases/genética , Mapeamento Encefálico , Isótopos de Carbono , Cocaína/análogos & derivados , Saúde da Família , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Mutação/genética , Proteínas Oncogênicas/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Proteína Desglicase DJ-1 , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismoRESUMO
OBJECTIVE: To establish a method for analyzing the PTEN-induced kinase 1 gene (PINK1) exon copy number and apply it to the analysis of PINK1 gene exon copy number variation (CNV) in patients with autosomal recessive early-onset Parkinsonism (AREP). METHODS: Real-time PCR was used to analyze the exon copy number in 22 probands with AREP from unrelated Chinese Han families and 30 healthy controls. RESULTS: Copy numbers of exons 1-8 of the PINK1 gene were analyzed, and satisfactory reaction conditions and primers for exons of the PINK1 gene were obtained. No exon CNV in the PINK1 gene was detected in this group. CONCLUSION: An analytical method for PINK1 gene exon copy number was established. The exon CNV in the PINK1 gene was rare in Chinese patients with AREP.
Assuntos
Éxons/genética , Dosagem de Genes/genética , Reação em Cadeia da Polimerase/métodos , Proteínas Quinases/genética , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Transtornos Parkinsonianos/genética , Adulto JovemRESUMO
Early onset parkinsonism (EOP) has been associated with mutations in the Parkin, PINK1, and DJ-1 genes. We studied the prevalence of mutations in all three genes in 127 unrelated Chinese patients with apparently sporadic EOP using direct sequencing analysis and real-time quantitative PCR analysis assay. There are 16 patients (12.6%) with mutations of Parkin gene, four patients (3.1%) with mutations of PINK1 gene, and three patients (2.4%) with mutation of DJ-1 gene. In conclusion, Parkin gene mutation is the most common pathogenic factor in Chinese patients with sporadic EOP. Mutations of DJ-1 and PINK1 gene are also found in Chinese patients with sporadic EOP.
Assuntos
Predisposição Genética para Doença/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação/genética , Proteínas Oncogênicas/genética , Doença de Parkinson/genética , Proteínas Quinases/genética , Ubiquitina-Proteína Ligases/genética , Adulto , Povo Asiático/etnologia , Povo Asiático/genética , China/etnologia , Análise Mutacional de DNA , Feminino , Marcadores Genéticos/genética , Predisposição Genética para Doença/etnologia , Testes Genéticos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/etnologia , Doença de Parkinson/metabolismo , Proteína Desglicase DJ-1 , Adulto JovemRESUMO
Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are known to cause typical, late-onset familial Parkinson's disease in different geographic origins. However, there was no report about mutations of LRRK2 gene in mainland China. The 51 coding exons and intron/exon boundaries of the LRRK2 gene were sequenced in nine families with Parkinson's disease. A novel LRRK2 missense mutation resulting in a single amino acid substitution K616R was present in one family with a dominant form of PD, and not in 200 controls. The patient presented with slowly progressive resting tremor, dyskinesia, and responded well to l-dopa. In conclusion, we identified a novel mutation in LRRK2 gene, which was the first mutation of LRRK2 found in the mainland Chinese population with familial Parkinson's disease.
Assuntos
Doença de Parkinson/genética , Proteínas Serina-Treonina Quinases/genética , Adulto , Idoso , Povo Asiático , China , Feminino , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Mutação , LinhagemRESUMO
OBJECTIVE: To investigate the mutation characteristics of ATP13A2 gene in Chinese patients with familial autosomal recessive early-onset parkinsonism (AREP). METHODS: Mutations of ATP13A2 gene were screened by polymerase chain reaction combined with DNA direct sequencing in patients with familial AREP. RESULTS: No pathogenic mutations in ATP13A2 gene were detected in this group. Six reported polymorphisms were identified. They were IVS6+70A>G, IVS12+66A>G, m.1849C>T, IVS20-56 G>A, m2671C>T and m2824G>A. CONCLUSION: ATP13A2 gene mutations may be rare in Chinese patients with familial autosomal recessive early-onset parkinsonism.
Assuntos
Povo Asiático/genética , Transtornos Parkinsonianos/epidemiologia , Transtornos Parkinsonianos/genética , ATPases Translocadoras de Prótons/genética , Adulto , Idade de Início , Sequência de Bases , China/epidemiologia , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação , Linhagem , Polimorfismo GenéticoRESUMO
Autosomal recessive early-onset Parkinsonism (AREP) has been associated with mutations in the Parkin, PINK1, DJ-1, and ATP13A2 genes. We studied the prevalence of mutations in all four genes in 29 Chinese unrelated families with AREP using direct sequencing analysis and real-time quantitative PCR analysis assay. There are 14 families (48.3%) with mutations of Parkin gene, 2 families (6.9%) with mutations of PINK1 gene, and 1 family (3.4%) with mutation of DJ-1 gene. No pathogenic mutations in ATP13A2 gene were found in these families. Three Parkin gene mutations (c.G859T, c.1069-1074delGTGTCC, and c.T1422C) and one DJ-1 gene mutation (c.T29C) have not been reported previously. In conclusion, Parkin gene mutation is the most common pathogenic factor in Chinese patients with AREP. Mutations of DJ-1 and PINK1 gene are also found in Chinese families with AREP. Mutations in ATP13A2 gene may be rare in Chinese families with AREP.
