We investigated 11 consanguineous families comprising 17 affected with recessively inherited young-onset parkinsonism for mutations both in the parkin and PINK1 gene.
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 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.
Twenty-nine of 109 probands with autosomal-recessive inheritance of parkinsonism (26.6%) were found to carry mutations in Parkin, PINK1, GBA, or HTRA2.
The PTEN-induced putative kinase 1 (PINK1) is a mitochondrially targeted serine-threonine kinase, which is linked to autosomal recessive familial parkinsonism.
The presence of these mutations appears to have an impact on the development of the parkinsonism, which can also occur in the heterozygous PINK1 mutation state.
Two new AREP loci (PARK6 and PARK7) have been recently mapped on chromosome 1p and confirmed in independent datasets, suggesting that both might be frequent.
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.
The foot dystonia and gait disorders seen at disease onset in affected members of our family, which were accompanied by parkinsonism had a similar clinical presentation to what has been described in previous reports of PINK1 mutation carriers.
Our data indicate that olfactory dysfunction is common in PINK1Parkinsonism and consists typically in defective odor identification and discrimination.
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.
Recent evidence from studies on the genetic forms of parkinsonism with particular stress on DJ-1, parkin, and PINK-1 also suggest the involvement of mitochondria and oxidative stress.
Mutations in seven genes are robustly associated with autosomal dominant (SNCA, LRRK2, EIF4G1, VPS35) or recessive (parkin/PARK2, PINK1, DJ1/PARK7) Parkinson's disease (PD) or parkinsonism.
Methylmercury can induce Parkinson's-like neurotoxicity similar to 1-methyl-4- phenylpyridinium: a genomic and proteomic analysis on MN9D dopaminergic neuron cells.