Genetic screening reveals high frequency of PARK2 mutations and reduced Parkin expression conferring risk for Parkinsonism in North West India

Abstract

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 in one patient. Parkin estimation was done by combination of immunolocalisation and FACS analysis revealing reduced Parkin expression among PD patients. The mutations in exons 1, 3 and 12 among sporadic PD patients were found to be higher among younger onset variants (age<45 years). This report also constitutes the first evidence that PARK 2 mutations contribute to the aberration in Parkin expression in blood leading to PD.

New Biomarker for Neovascular Age-Related Macular Degeneration: Eotaxin-2

“…Hypertension may increase the oxidative stress known to be associated with AMD resulting in expression of CCL24 in choroidal endothelial cells and its ligands in RPE (Chong et al, 2008). Notwithstanding AMD as an eye disorder, the analysis of serum is consistent with several previous reports in both retina and brain (Sharma et al, 2009;Baas et al, 2010;Vinish et al, 2010). Therefore, CCL24 could represent a novel biomarker for early detection of CNV with potential to be targeted as a new therapeutic entity through future studies.…”

Roll on genetics of PARK and Parkinsonism in the developing world

“…The frequency of parkin mutations of 40.5% in the study by Vinish et al 3 is significantly higher than previously reported values of 7.2–12.5% from developing countries 2. Whereas studies from Sub-Saharan Africa did not find any pathogenic mutations in the parkin gene,4 the very high frequency of mutations in the current study is close to values reported among Europeans and may be due to the migrant origin of the ethnically homogenous North Indians.…”

“…The PARK genotypes, however, have not all been linked to proven Lewy body pathology or nigral degeneration2 as evident in dementia with Lewy bodies or PD with dementia (table 1). In this issue, Vinish et al 3 provide interesting data on the profile of parkin mutations in North Indian subjects with PD ( see page ) .…”

Movement disorders: Indian scenario: A clinico-genetic review

“…[44] Parkinson's Disease Eighteen genetic loci with 13 underlying genes have been identified till date for PD, however, only 6 genes [Alpha-synuclein (SNCA), Leucine rich repeat kinase-2 (LRRK2), Parkin, PTEN induced putative kinase 1 (PINK1), DJ-1, ATPase type 13A2 (ATP13A2)] could be conclusively proved to be causal towards the disease. [45] In India, candidate gene studies have been performed on SNCA, [46,47] Parkin, [48][49][50][51][52] PINK1, [53] DJ-1, [54,55] and LRRK2 [47,[56][57][58][59] only [ In India studies to understand the molecular basis of PD is rapidly getting pace. A number of association studies have been reported on the candidate [53,60] as well as the susceptibility genes involved in dopamine metabolism, [61][62][63] xenobiotic metabolism, [64,65] neuronal cytoskeletal stability [66,67] etc., from different parts of India.…”