These results suggest that deletions in the parkin gene will be found in other families besides those of Japanese origin and that there must be at least one additional locus responsible for early onset autosomal recessive Parkinson's disease.
A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe. French Parkinson's Disease Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease.
Now, we report the subcellular localization of Parkin protein in patients with AR-JP or Parkinson's disease (PD) and in controls by immunoblotting and immunohistochemistry using antibodies raised against the Parkin molecule.
To date, two causative genes, alpha-synuclein and the parkin gene, have been identified. alpha-Synuclein is involved in the pathogenesis of an autosomal dominant form of PD and constitutes a major component of the Lewy body, which is a pathological hallmark of idiopathic PD.
Mutations in the parkin gene are a major cause of early-onset autosomal recessive familial Parkinson's disease and isolated juvenile-onset Parkinson's disease (at or before the age of 20 years).
We conclude that the phenotypic spectrum associated with mutations in the parkin gene is broader than previously reported, suggesting that this gene may be important in the etiology of the more frequent late-onset typical Parkinson's disease.
Our data suggest that the parkin gene is important in early-onset PD and that multiple genetic factors may be important in the development of idiopathic late-onset PD.
The parkin gene and its phenotype. Italian PD Genetics Study Group, French PD Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease.
Mutations in the parkin gene causal of autosomal recessive juvenile parkinsonism highlight that ubiquitin-mediated proteolysis may play an important role in the pathobiology of PD.
These data suggest that compound heterozygous parkin mutations and loss of parkin protein may lead to early-onset parkinsonism with Lewy body pathology, while a hemizygous mutation may confer increased susceptibility to typical Parkinson's disease.
The parkin gene on chromosome 6q and loci on chromosome 1p35-36 and 1p36 are responsible for some cases of autosomal recessive early-onset parkinsonism, but they do not appear to influence susceptibility or variability of age at onset for idiopathic PD.
The point mutations on exon 2 of parkin gene were detected using polymerase chain reaction(PCR), agarose electrophoresis, single strand conformation polymorphism(SSCP), DNA sequencing and analysis of restrict enzyme in DNA of 60 Parkinson's disease patients with an onset age under 50 and 120 normal controls.
According to our data, the genetic variation at the PARKIN gene (including promoter polymorphisms) did not contribute to the risk of developing PD in the general population.