PINK1 (PARK6) associated Parkinson disease in Ireland

Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London, UK.
Neurology (Impact Factor: 8.3). 11/2004; 63(8):1486-8. DOI: 10.1212/01.WNL.0000142089.38301.8E
Source: PubMed

ABSTRACT Mutations in the PINK1 gene have recently been shown to cause autosomal recessive Parkinson disease (PD). The authors assessed the prevalence of PINK1 gene mutations in 290 well-characterized early- and late-onset PD patients from Ireland. In a 51-year-old PD patient with a family history of PD, the authors identified a novel heterozygous mutation (R147H) in exon 2 of the PINK1 gene. Overall, these data indicate that PINK1 mutations are a rare cause of PD in Ireland.


Available from: Owen A Ross, Jan 17, 2014
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    ABSTRACT: Parkinson's disease is a progressive neurodegenerative disorder, where most cases are sporadic with a late onset. In rare incidences familial forms of early-onset parkinsonism occur, and when recessively inherited, cases are often explained by mutations in either the parkin (PARK2) or PINK1 (PARK6) gene or on exceptional occasions the DJ-1 (PARK7) or ATP13A2 (PARK9) gene. Recessively inherited deletions/duplications and point mutations in the parkin gene are the most common cause of early-onset parkinsonism known so far, but in an increasing number of studies, genetic variations in the serine/threonine kinase domain of the PINK1 gene are found to explain early-onset parkinsonism. In this study all families were from a population with a high incidence of consanguinity. We investigated 11 consanguineous families comprising 17 affected with recessively inherited young-onset parkinsonism for mutations both in the parkin and PINK1 gene. Exons and flanking regions were sequenced, and segregation patterns of genetic variation were assessed in members of the respective families. An exon dosage analysis was performed for all exons in both genes. In the parkin gene, a three generation family was identified with an exon 4 deletion segregating with disease. Both affected were homozygous for the deletion that segregated on a haplotype that spanned the gene in a haplotype segregation analysis that was performed using additional markers. Exon dosage analysis confirmed the recessive pattern of inheritance with heterozygous deletions segregating in healthy family members. In the PINK1 gene we identified two novel putative pathogenic substitutions, P416R and S419P, located in a conserved motif of the serine/threonine kinase domain. Both substitutions segregated with disease in agreement with a recessive pattern of inheritance within respective families and both were present as homozygous in two affected each. We also discuss common polymorphisms in the two genes found to be co-segregating within families. Our results further extend on the involvement of PINK1 mutations in recessive early-onset parkinsonism with clinical features similar to carriers of parkin mutations.
    BMC Neurology 01/2009; 8:47. DOI:10.1186/1471-2377-8-47 · 2.49 Impact Factor
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    ABSTRACT: Background Parkinson's disease (PD) continues to be an important neurological disorder. It is caused by the loss of dopaminergic neurons in the substantia nigra. Dopamine, the neurotransmitter produced from dopaminergic neurons, is a major precursor of endogenous morphine. There are approximately 18 genes associated with PD; their roles have not yet been completely established. PARK2 is a gene that encodes for the protein parkin, and PINK1 is a gene that encodes for PTEN-induced putative kinase 1. Material and Methods Our objective was to determine if morphine treatment of HTB-11 cells affects the expression of PINK1 and PARK2. HTB-11 cells were treated with 10-7 M morphine for 2 h and a microarray analysis was conducted. To verify the microarray analysis, 3 Q-PCR trials were run using 10-6 M naloxone, morphine (10-7 M), or a naloxone/morphine mix. Results In both the microarray analysis and the Q-PCR analysis, PARK2 was up-regulated and PINK1 was down-regulated. Conclusions Morphine can affect the expression of PD-associated genes.
    05/2014; 20:63-9. DOI:10.12659/MSMBR.890557
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    ABSTRACT: La malattia di Parkinson è la seconda patologia neurodegenerativa per frequenza ed è caratterizzata da una perdita progressiva dei neuroni dopaminergici e da un accumulo di corpi di Lewy. In questi ultimi 10 anni l’identificazione di almeno 13 loci e 9 geni (Parkina, PINK1, DJ-1, ATP13A2, SNCA, UCHL1, LRRK2, GIGYF2 e Omi/HTRA2) implicati nelle forme familiari e sporadiche del morbo di Parkinson ha permesso di comprendere meglio la fisiopatologia di questa complessa entità. Le forme monogeniche hanno una frequenza variabile a seconda dell’origine etnica delle popolazioni studiate. Un effetto di dose del gene è osservato per il gene SNCA e il fenotipo dei portatori delle mutazioni è spesso quello di una sindrome parkinsoniana tipica. La penetranza di alcune mutazioni dipende dall’età e, a volte, è incompleta. Alcuni geni implicati nelle forme monogeniche della malattia di Parkinson sono anche fattori di rischio in alcuni casi sporadici.
    01/2010; 10(2):1–9. DOI:10.1016/S1634-7072(10)70497-9