Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1

@article{Valente2004HereditaryEP,
  title={Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1},
  author={Enza Maria Valente and Patrick M. Abou-Sleiman and Viviana Caputo and Miratul M. K. Muqit and Kirsten Harvey and Suzana Gispert and Zeeshan Ali and Domenico Del Turco and Anna Rita Bentivoglio and Daniel G. Healy and Alberto Albanese and Robert Luke Nussbaum and Rafael González-Maldonado and Thomas Deller and Sergio Salvi and Pietro Cortelli and William P. Gilks and D. S. Latchman and Robert J. Harvey and Bruno Dallapiccola and Georg Auburger and Nicholas W. Wood},
  journal={Science},
  year={2004},
  volume={304},
  pages={1158 - 1160}
}
Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons in the substantia nigra. We previously mapped a locus for a rare familial form of PD to chromosome 1p36 (PARK6). Here we show that mutations in PINK1 (PTEN-induced kinase 1) are associated with PARK6. We have identified two homozygous mutations affecting the PINK1 kinase domain in three consanguineous PARK6 families: a truncating nonsense mutation and a missense mutation at a highly… 
Mutational analysis of the PINK1 gene in early-onset parkinsonism in Europe and North Africa.
TLDR
It is suggested that PINK1 is the second most frequent causative gene in early-onset Parkinson's disease with a slowly progressive phenotype, indistinguishable from early-ONSet patients with parkin mutations.
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The monogenic variants are important tools in identifying cellular pathways that also shed light on the molecular pathogenesis of sporadic PS and some of these genes may play a role in the etiology of the common sporadic form of PS.
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TLDR
Three genes have been identified to cause autosomal-recessive early-onset parkinsonism: parkin, DJ1, and PINK1, which are thought to be involved in the proteasomal protein degradation pathway, in the cell’s response to oxidative stress, and in mitochondrial function.
Recessive Parkinson's disease
TLDR
Recent advances in knowledge about genes associated with recessive PD, including parkin, PINK1, and DJ‐1 are reviewed, suggesting that these gene products share a common pathway to nigral degeneration in both familial and sporadic PD.
Update on the genetics of Parkinson's disease
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  • Biology
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  • 2007
TLDR
Evidence is emerging that at least some of these genes may play a direct role in the etiology of the common sporadic form of Parkinson's disease, and the cellular pathways identified in rare monogenic variants of the disease also shed light on the molecular pathogenesis in typical sporadic PD.
Analysis of the PINK1 gene in a large cohort of cases with Parkinson disease.
TLDR
Autosomal recessive mutations in PINK1 are a rare cause of young-onset Parkinson disease, including the first reported compound heterozygous mutation (Glu240Lys and Leu489Pro) and a homozygous Leu347Pro mutation in 2 unrelated young-ONSET Parkinson disease patients.
Genetics of familial Parkinson's disease
TLDR
The identification of mutations in a-synuclein (SNCA), parkin (PARK2), ubiquitin C-terminal hydrolase L1 (UCHL1), PTEN-induced kinase 1 (PINK1), DJ-1, nuclear receptorrelated 1 (Nurr1) and leucine-rich repeat kinase 2 (LRRK2) genes has confirmed the role of genetics in familial forms of PD.
Pathogenesis of familial Parkinson’s disease: new insights based on monogenic forms of Parkinson’s disease
TLDR
Recent progress in knowledge about the genes associated with familial PD is reviewed, revealing that PD‐associated genes play important roles in cellular functions, such as mitochondrial functions, ubiquitin‐proteasomal system, autophagy‐lysosomal pathway and membrane trafficking.
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