Parkin mutations in familial and sporadic Parkinson's disease among Indians.
ABSTRACT We observed a mutation frequency of 8.5% in Parkin gene among Indian PD patients based on sequencing and gene dosage analysis of its exons. We identified nine point mutations of which seven are novel and hitherto unreported. These mutations accounted for 14.3% familial PD, 6.9% young onset and 5.9% late onset sporadic PD. Of the 20 PD patients with mutations only two had homozygous mutations and one was a compound heterozygote. Homozygous exonic deletions were absent but heterozygous exon rearrangements were observed in 9.2% of patients (19% familial PD and 4.5% young onset sporadic PD).
SourceAvailable from: Ramesh Narasingappa
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ABSTRACT: Movement disorder (MD) is an important branch of neurology and has great potentiality in management because of improved diagnosis and therapeutic strategies. Over the last three decades, emphasis has been laid on the evaluation of various MDs in India by a limited number of interested neurologists and basic scientists. In this review, we want to highlight common problems of MDs in India with regard to epidemiology, clinical features and genetics.Neurology India 09/2013; 61(5):457-466. DOI:10.4103/0028-3886.121908 · 1.08 Impact Factor
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ABSTRACT: Pesticide/neurotoxin/free radical-induced oxidative stress leading to dopaminergic neuronal vulnerability is known to promote sporadic Parkinson's disease (PD). This study investigated the contribution of polymorphisms in genes from drug-metabolizing enzymes (DMEs) and the oxidative stress pathway to PD susceptibility and severity among a north Indian cohort. Three hundred and thirty-nine PD patients diagnosed using UK PD brain bank criteria and 344 age-, sex-, and ethnicity-matched controls were recruited. Univariate and multivariate analyses were carried out to test allelic, genotypic, and haplotypic associations, and gene-gene interactions were assessed for 18 polymorphisms from 13 genes. Disease severity was calculated on the basis of the Hoehn and Yahr (HY) scale and Unified Parkinson's Disease Rating Scale III scores and was compared among the genotypic categories of markers. An association of GSTO1-rs4925 (P=0.04) and NQO1-rs1800566 (P=0.02) in univariate and multivariate analysis (P=0.01 and P=0.03, respectively) with disease susceptibility was observed. Significant and novel association of PON2-rs7493 (P=0.00009 with UPDRS III, P=0.003 with HY) with disease severity was retained after Bonferroni correction. On categorizing the cohort into young-onset PD (YOPD, n=90 cases, 104 controls) and late-onset PD ( n=249 cases, 240 controls), the association of several single nucleotide polymorphisms (SNPs) in DMEs was observed with YOPD. The association of NQO1, PON2, and DME genes (this study) and NAT2 (previous study) with PD among Indians may point toward an inherent population-specific genetic predisposition. This, probably compounded by an increase in environmental toxins and the indiscriminate use of pesticides in our country in the last few decades, may suggest likely gene-environment interactions, which may explain the increasing incidence of YOPD among Indians.Pharmacogenetics and Genomics 12/2011; 21(12):790-7. DOI:10.1097/FPC.0b013e32834bcd74 · 3.45 Impact Factor