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Mutations of the parkin gene are the most frequent cause of early onset autosomal recessive parkinsonism (EO-AR). Here we show that inactivation of the parkin gene in mice results in motor and cognitive deficits, inhibition of amphetamine-induced dopamine release and inhibition of glutamate neurotransmission. The levels of dopamine are increased in the(More)
Parkin knockout (KO) mice show behavioural and biochemical changes that reproduce some of the presymptomatic aspects of Parkinson's disease, in the absence of neuronal degeneration. To provide insight into the pathogenic mechanisms underlying the preclinical stages of parkin-related parkinsonism, we searched for possible changes in the brain proteome of(More)
To establish phenotype-genotype correlations in early-onset parkinsonism, we have compared the phenotype of a large series of 146 patients with and 250 patients without parkin mutations. Although no single sign distinguished the groups, patients with mutations had significantly earlier and more symmetrical onset, dystonia more often at onset and(More)
Parkin gene mutations are reported to be a major cause of early-onset parkinsonism (age at onset < or = 45 years) in families with autosomal recessive inheritance and in isolated juvenile-onset parkinsonism (age at onset <20 years). However, the precise frequency of parkin mutations in isolated cases is not known. In order to evaluate the frequency of(More)
Mutations in the Parkin gene cause juvenile and early onset Parkinsonism. While Parkin-related disease is presumed to be an autosomal-recessive disorder, cases have been reported where only a single Parkin allele is mutated and raise the possibility of a dominant effect. In this report, we re-evaluate twenty heterozygous cases and extend the mutation(More)
Autosomal recessive juvenile parkinsonism (AR-JP) is a form of hereditary parkinsonism characterized by variable clinical presentations and caused by mutations in a novel gene, parkin, on chromosome 6q25.2-27. Until now, no Russian cases of parkin-associated AR-JP have been reported on. We recruited 16 patients from 11 Russian families with dopa-responsive(More)
The authors report an Italian family with pseudo-dominant inheritance of parkinsonism attributable to parkin gene mutations. The father (disease onset at age 57 years) was homozygous for a triplication of exon 2 that is so far unique. The unaffected mother was heterozygous for deletions of exons 3 and 4, and the son (onset at age 31 years) was a compound(More)
A wide variety of mutations in the parkin gene, including exon deletions and duplications, as well as point mutations, result in autosomal recessive early-onset parkinsonism. Interestingly, several of these anomalies were found repeatedly in unrelated patients and may therefore result from recurrent, de novo mutational events or from founder effects. In the(More)
The frequency of parkin mutations was evaluated in 30 families of highly diverse geographic origin with early-onset autosomal recessive parkinsonism. Twelve different mutations, six of which were new, were found in 10 families from Europe and Brazil. Patients with parkin mutations had significantly longer disease duration than patients without the mutation(More)
The objective was to describe a family with autosomal recessive, early onset parkinsonism, with affected siblings carrying three different exon rearrangements in the parkin gene. The living affected siblings were personally examined. Molecular genetic analyses included exon dosage of the parkin gene using a semiquantitative multiplex polymerase chain(More)
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