Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1
Medway School of Pharmacy · Ospedale Regina Margherita · +9 more institutions
Abstract
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 conserved amino acid. Cell culture studies suggest that PINK1 is mitochondrially located and may exert a protective effect on the cell that is abrogated by the mutations, resulting in increased susceptibility to cellular…
Citation impact
- FWCI
- 109.69
- Percentile
- 100%
- References
- 19
Authors
22- EMEnza Maria ValenteCorresponding
Medway School of Pharmacy, Ospedale Regina Margherita, National Hospital for Neurology and Neurosurgery, University College London, Sapienza University of Rome
- PMPatrick M. Abou‐SleimanCorresponding
Medway School of Pharmacy, Ospedale Regina Margherita, National Hospital for Neurology and Neurosurgery, University College London, Sapienza University of Rome
- VCViviana CaputoCorresponding
Medway School of Pharmacy, Ospedale Regina Margherita, National Hospital for Neurology and Neurosurgery, University College London, Sapienza University of Rome
- MMMiratul M. K. MuqitCorresponding
Medway School of Pharmacy, Ospedale Regina Margherita, National Hospital for Neurology and Neurosurgery, University College London, Sapienza University of Rome
- KHKirsten Harvey
Medway School of Pharmacy, Ospedale Regina Margherita, National Hospital for Neurology and Neurosurgery, University College London, Sapienza University of Rome
Topics & keywords
- PINK1
- LRRK2
- Missense mutation
- Genetics
- Nonsense mutation
- Substantia nigra
- Biology
- Mutation
- Good health and well-being