RESUMO
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
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
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.