Recent studies have demonstrated that mutations in PINK1 (PARK6 locus) gene, encoding PTEN-induced kinase 1, are associated with both familial recessive and sporadic early onset parkinsonism.
To investigate a possible association of mutations in the PTEN-induced putative kinase 1 (PINK1) gene with psychiatric disorders in a large family with monogenic parkinsonism.
We discuss the roles of heterozygous LRRK2 mutations and heterozygous parkin and PINK1 mutations in the development of parkinsonism, and propose an integrated aetiological model for this complex disease.
Mutations in five causative genes combined [alpha-Synuclein (SNCA), Parkin, PTEN-induced kinase 1 (PINK1), DJ-1, Leucine-rich repeat kinase 2 (LRRK2)] account for 2-3% of all cases with classical parkinsonism, often clinically indistinguishable from idiopathic Parkinson's disease.
Mutations in PINK1 (PTEN-induced putative kinase 1) are causal for early onset recessive parkinsonism in humans, characterized by damage to the nigrostriatal system.
To decipher the role of PINK1 in pathogenesis of Parkinson's disease (PD), researchers need to identify protein substrates of PINK1 kinase activity that govern neuronal survival, and establish whether aberrant regulation and inactivation of PINK1 contribute to both familial Parkinsonism and idiopathic PD.
Loss-of-function mutations in the PTEN-induced kinase 1 (PINK1) or parkin genes, which encode a mitochondrially localized serine/threonine kinase and a ubiquitin-protein ligase, respectively, result in recessive familial forms of Parkinsonism.
Here, we describe a novel homozygous mutation (Q126P), identified in two affected German sisters with a clinical phenotype typical for PINK1-associated parkinsonism.
Here, we describe a novel homozygous mutation (Q126P), identified in two affected German sisters with a clinical phenotype typical for PINK1-associated parkinsonism.
These findings further expand the clinical spectrum of PINK1-related parkinsonism to include late onset, typical PD, and underline the existing difficulties in discriminating between mendelian parkinsonism and idiopathic PD.
These findings further expand the clinical spectrum of PINK1-related parkinsonism to include late onset, typical PD, and underline the existing difficulties in discriminating between mendelian parkinsonism and idiopathic PD.