RESUMO
We analysed the parkin gene in a large consecutive series (146) of unrelated early onset Parkinson's disease (onset ?40 years of age) patients. Twelve cases (8.2%) had homozygous or compound heterozygous point mutations and/or exon rearrangements, while a single mutation was found in four subjects (2.7%). We identified eight exon rearrangements and nine point mutations, two of which were novel: c.735delT (p.C212/X224) and c.815C>G (p.C238W). Genotype-phenotype correlation revealed that parkin carriers had features similar to those of non-carrier early onset Parkinson disease patients.
Assuntos
Predisposição Genética para Doença , Mutação/genética , Doença de Parkinson/genética , Ubiquitina-Proteína Ligases/genética , Adulto , Idade de Início , Análise Mutacional de DNA , Éxons/genética , Feminino , Dosagem de Genes , Frequência do Gene , Genótipo , Humanos , Masculino , Fenótipo , Índice de Gravidade de Doença , Estatísticas não ParamétricasRESUMO
We analysed the Leucine-Rich Repeat Kinase 2 (LRRK2) gene for the G2019S mutation in 1245 consecutive, unrelated patients with primary degenerative parkinsonism, and collected information on medical history, motor, cognitive and neuropsychiatric functions to characterize the clinical phenotype associated to the G2019S mutation. The mutation was detected in heterozygous state in 19 probands (1.7%), and in five additional affected relatives. Clinical features in carriers were those of typical, idiopathic Parkinson's disease. However, behavioural abnormalities were frequent (87%), suggesting a more widespread limbic involvement in G2019S carriers.
Assuntos
Doença de Parkinson/epidemiologia , Doença de Parkinson/genética , Mutação Puntual , Proteínas Serina-Treonina Quinases/genética , Adulto , Idade de Início , Cognição , Feminino , Predisposição Genética para Doença/epidemiologia , Testes Genéticos , Heterozigoto , Humanos , Itália/epidemiologia , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/epidemiologia , Transtornos do Humor/genética , Atividade Motora , Testes Neuropsicológicos , Fenótipo , PrevalênciaRESUMO
We analyzed the DJ1 gene in a large consecutive series (N=163) of Italian unrelated Early Onset Parkinson Disease (EOPD: onset ≤40 years of age) patients and 100 healthy controls (mean age 64 ± 7 years). No homozygous or compound heterozygous mutations with an obvious pathogenic effect were found. Several variants were identified, some of which were novels. All variants had similar frequency in patients and in controls. Our data suggest that DJ1 mutations are very rare in Italian EOPD. Other genes and risk factors for PD are still to be identified.