Abstract
The identification of Mendelian mutations in rare forms of familial Parkinson’s disease (PD) have provided significant insights into the molecular pathogenesis of this common complex disorder. DJ-1 is the third of four genes known to be definitively causal in familial PD, the three others being α-synuclein, parkin and the recently identified PINK1. Mutations in the DJ-1 gene were identified in two European families, a Dutch kindred harbouring a large homozygous genomic deletion encompassing exons 1–5 of the gene and an Italian kindred with a homozygous L166P missense mutation. The clinical phenotype of the two families was similar to that of parkin cases. Age of onset was in the mid-thirties with good responsiveness to l-dopa and slow disease progression. Focal dystonias and blepharospasm were also evident as were behavioural disturbances early in the course of the disease. To date, there are no studies of pathological material from known DJ-1 patients. It therefore remains to be determined whether these patients form Lewy bodies and/or Lewy neurites, the eosinophilic fibrillary inclusions that contain predominantly α-synuclein and that are the pathological hallmark of PD.
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Abou-Sleiman, P.M., Healy, D.G. & Wood, N.W. Causes of Parkinson’s disease: genetics of DJ-1. Cell Tissue Res 318, 185–188 (2004). https://doi.org/10.1007/s00441-004-0922-6
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DOI: https://doi.org/10.1007/s00441-004-0922-6