Four PINK1 homozygous mutations, three novel (Q129X, Q129fsX157, G440E, and one previously reported; Q456X), segregate with parkinsonism in 46 individuals in 14 of 92 families (15%).
Genetic atypical Parkinson's disease (PD) describes monogenic forms of PD that resemble idiopathic PD but feature prominent atypical clinical signs and symptoms and can be sub-grouped into i) atypical monogenic forms caused by mutations in the ATP13A2, DNAJC6, FBXO7, SYNJ1, VPS13C, and DCTN genes; ii) monogenic PD more closely resembling idiopathic PD, but associated with atypical features in at least a subset of cases (SNCA-, LRRK2-, VPS35-, Parkin-, PINK1-, and DJ-1-linked PD; iii) carriers of mutations in genes that are usually associated with other movement disorders but may present with parkinsonism, such as dopa-responsive dystonia.
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.
In the present study we analysed fibroblasts from a patient carrying the homozygous mutation p.W437X in the PTEN-induced kinase 1 (PINK1), which manifested a very early onset parkinsonism.
In three forms, caused by mutations in parkin (PARK2), PINK1 (PARK6), or DJ-1 (PARK7), the phenotype is usually characterized by levodopa-responsive parkinsonism without atypical features.
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.
Low doses of paraquat and polyphenols prolong life span and locomotor activity in knock-down parkin Drosophila melanogaster exposed to oxidative stress stimuli: implication in autosomal recessive juvenile parkinsonism.
Methylmercury can induce Parkinson's-like neurotoxicity similar to 1-methyl-4- phenylpyridinium: a genomic and proteomic analysis on MN9D dopaminergic neuron cells.
Mutation of hop-1 and pink-1 attenuates vulnerability of neurotoxicity in C. elegans: the role of mitochondria-associated membrane proteins in Parkinsonism.
Mutations associated with early-onset autosomal recessive parkinsonism have been identified in the Parkin gene, and recently a second gene, PARK6, involved in early-onset recessive parkinsonism was localized on chromosome 1p35-36.
Mutations in PINK1 (PTEN-induced putative kinase 1) are causal for early onset recessive parkinsonism in humans, characterized by damage to the nigrostriatal system.
Mutations in DJ-1, PINK1 (PTEN-induced putative kinase 1) and parkin all cause recessive parkinsonism in humans, but the relationships between these genes are not clearly defined.
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.