PARK 2 mutation causes PD

PARK 2 mutations cause Parkinsonism (PD) in North West Indian Patients



Among several etiological factors, PARK2 mutations are the most common cause of Parkinson’s disease (PD), resulting in degeneration of dopaminergic neurons in the substantia nigra. In order to examine the contribution of PARK2 mutations and corresponding Parkin expression in blood of North West Indian PD patients, we screened 120,000 patients from 2001 to 2006 for features of PD, and tested PARK2 mutations in 69 of those that fulfilled the UKPDBBC citeria. 43 controls lacking extrapyramidal signs were also analysed.

The PCR analysis revealed the occurrence of homozygous deletions in 28 of 69 samples analysed (40.5%) represented by exon-1 (15.9%), exon-3 (11.5%), and exon-12 (11.5%). Sequencing revealed point mutations in exon 4 and exon 9 in six of these patients (8.7%) including one novel missense Gly1083Trp mutation. Parkin estimation was done by combination of immunolocalisation studies and FACS analysis revealing reduced Parkin expression among those that possessed mutations. The mutation frequency in exons 1, 3, and 12 among sporadic PD patients was found to be higher among younger onset variants. This report also constitutes the first evidence that PARK 2 mutations contribute to the aberration in Parkin expression in blood leading to PD.


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