Complex relationship between Parkin mutations and Parkinson disease

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Abstract
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 haploinsufficiency may be sufficient for disease in some cases.