Complex relationship between Parkin mutations and Parkinson disease.
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 screening to include the promoter and intron/exon boundaries. Novel deletion, point and intronic splice site mutations are described, along with promoter variation. These data, coupled with a complete review of published Parkin mutations, confirms that not only is recessive loss of Parkin a risk factor for juvenile and early onset Parkinsonism but that Parkin haplo-insufficiency may be sufficient for disease in some cases.
West, A; Periquet, M; Lincoln, S; Lücking, CB; Nicholl, D; Bonifati, V; Rawal, N; Gasser, T; Lohmann, E; Deleuze, J-F; Maraganore, D; Levey, A; Wood, N; Dürr, A; Hardy, J; Brice, A; Farrer, M; French Parkinson's Disease Genetics Study Group and the European Consortium on Genetic Susceptibility on Parkinson's Disease,
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