Molecular pathogenesis of Parkinson's disease: Identification of mutations in the Parkin gene in Indian patients

Biswas, Arindam; Gupta, Arnab; Naiya, Tufan; Das, Gourab; Neogi, Rajarshi; Datta, Somnath; Mukherjee, Subhas; Das, Shyamal Kumar; Ray, Kunal; Ray, Jharna

doi:10.1016/j.parkreldis.2006.04.005

Cited by 34 publications

(21 citation statements)

References 25 publications

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“…It is possible that these factors modify the Parkin translational machinery in such patients independent of Park2 mutations. Although studies from Indian population detected deletions in exons 3-4 (two siblings in 138 patients; 1.449%) 4 and exons 8-9 (one in 102 patients; 0.98%), 3 it can be concluded to the occurrence of low frequency of deletions in the cohorts studied, similar to our findings, quite contrary to heterozygous exon rearrangements observed in 9.2% of North Indian population while absence of homozygous exonic deletions. 5 Some possible limitations of our study should be acknowledged.…”

Section: Discussionsupporting

confidence: 81%

Evaluation of PARKIN gene variants in West Bengal Parkinson’s disease patients

et al. 2015

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Little information is available regarding the molecular pathogenesis of Parkinson's disease (PD) among the Bengalee population in West Bengal, India. This study was undertaken to determine the contribution of Parkin variants in well-defined ethnically identical Bengalee population of India and further to describe the clinical spectrum associated with these mutations. A total of 150 unrelated PD patients and 150 controls were recruited for the study. The entire cohort was screened for mutations in all the 12 exons of the gene along with flanking splice junctions by polymerase chain reaction and DNA sequencing. Eleven nucleotide variants including two novel changes were detected. Cerebrospinal fluid (CSF) parkin protein expression of the novel mutation, Val186Ile (found in heterozygous condition in one patient only) was almost 2.7 folds lower than the controls and other PD patients. Molecular characterization of polymorphisms Ser167Asn and Val380Leu depicted that homozygous Ser167 and Val380 are significantly associated with the disease. We did not find any linkage disequilibrium among the SNPs, the low r(2) for every pair of single-nucleotide polymorphisms (SNPs) indicated that these SNPs cannot be tagged by each other. Another novel intronic change, IVS8+48C>T was present in almost equally in PD patients and controls. Among the ethnically defined Bengalee population of West Bengal, occurrence of Parkin mutation is 4% (6/150) of the PD patient pool supported with decreased folds of expression of CSF PARKIN protein. Parkin polymorphisms, Ser167 and Val380 are risk factors for the progression of the disease, and their frequency is greatly influenced by ethnic origin.

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Section: Discussionsupporting

confidence: 81%

Evaluation of PARKIN gene variants in West Bengal Parkinson’s disease patients

et al. 2015

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“…Three reported (R334C, Ex2-3del, and Ex5del) L€ ucking et al, 2000;Biswas et al, 2006] and a novel c.1084intron þ (86 or 90-bp insertion) mutations were identified (Fig. 1A).…”

Section: Mutation/variant Analysis Of Parkinmentioning

confidence: 92%

Genetic analysis of Parkin in early onset Parkinson's disease (PD): Novel intron 9 g > a single nucleotide polymorphism and risk of Taiwanese PD

Chao

et al. 2009

American J of Med Genetics Pt B

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Early onset Parkinson's disease (PD) has been associated with mutations in Parkin. We screened Parkin mutations in a cohort of Taiwanese early onset PD using direct cDNA sequencing. Two deletions (Ex2-3del and Ex5del), one point mutation (R334C), one 86-bp IVS9 insertion (c.1084intron(+)), and two polymorphisms (S167N and V380L) were identified. The mutations identified are heterozygous and none of the mutation carriers possess two Parkin mutations. The c.1084intron(+) was due to a novel IVS9 g > a change. To assess the association of IVS9 g > a, S167N and V380L with the risk of PD, we conducted a case-control study in a cohort of PD and ethnically matched controls. Although the difference is not significant, the V380L C allele frequency was notably lower in PD patients than the controls and a trend toward decrease in risk of developing PD was evident (odds ratio: 0.71, 95% confidence interval: 0.53-0.97, P = 0.029). Contrarily the IVS9 g > a a allele frequency was notably higher in PD patients than the controls and a trend toward increase in risk of developing PD was also evident (odds ratio: 1.65, 95% confidence interval: 1.06-2.59, P = 0.028). Quantitative real-time PCR showed that the relative Parkin c.1084intron(+) mRNA expression was increased in PD patients with IVS9 ga genotype as compared to gg genotype. Pairwise genotype analysis revealed that IVS9 gg genotype strengthens the negative association of the V380L GC genotype with PD (odds ratio: 0.67, 95% confidence interval: 0.48-0.94, P = 0.021). The results of Parkin mutation/polymorphism screening may contribute to our understanding of PD.

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“…For quick screening of nucleotide variants, PCR products were subjected to Single Stranded Conformation Polymorphism (SSCP) analysis, as described previously [2,16]. The DNA fragments showing band shifts were subjected to bi-directional DNA sequencing to identify nucleotide variants as compared to the wild-type DJ-1 gene sequence (GenBank ID: AB015652).…”

Section: Screening Of the Dj-1 Genementioning

confidence: 99%

“…The cohort has previously been screened for Parkin [2], PINK1 [3] and prevalent/ common mutations of LRRK2 (p.Arg1441Cys, p.Arg1441Gly, p.Arg1441His, p.Tyr1699Cys, p.Ile2012Thr, p.Gly2019Ser and p. Ile2020Thr) [17]. No suspect variant was identified in LRRK2 causal to PD in our cohort.…”

Section: Dj-1 Mutation Screeningmentioning

confidence: 99%

DJ-1Variants in Indian Parkinson’s Disease Patients

Sadhukhan

Biswas²,

Das³

et al. 2012

Disease Markers

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Abstract. Parkinson's disease (PD) is a common neurodegenerative movement disorder. Among the candidate genes, DJ-1 accounts for about 1% of the cases in different populations. We aim to find the contribution of the gene towards PD among Indians. By screening DJ-1 in 308 PD patients of eastern India and 248 ethnically matched controls, a total of 21 nucleotide variantsincluding two nonsynonymous changes -were detected. p.Arg98Gln was identified in 6 unrelated patients and 2 controls while p.Val35Ile, a novel change, was found only in 2 unrelated patients. A SNP (rs7517357) was observed to be moderately associated with increased risk of PD (p < 0.05). The deletion allele (g.168 185del) of a known 18 bp del/ins/dup polymorphism was found to be over represented (p < 0.05) among older patients (> 40 years) compared to the controls (> 45 years). Two of the patients, also heterozygotes for PINK1 mutation, had more severe disease phenotypes, consistent with the reported interaction between PINK1 and DJ-1 gene products [19]. Our results demonstrate that up to 3.9% (12/308) of PD patients of eastern India harbor DJ-1 variants that should be explored further for any causal relationship with PD.

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Molecular pathogenesis of Parkinson's disease: Identification of mutations in the Parkin gene in Indian patients

Cited by 34 publications

References 25 publications

Evaluation of PARKIN gene variants in West Bengal Parkinson’s disease patients

Evaluation of PARKIN gene variants in West Bengal Parkinson’s disease patients

Genetic analysis of Parkin in early onset Parkinson's disease (PD): Novel intron 9 g > a single nucleotide polymorphism and risk of Taiwanese PD

DJ-1Variants in Indian Parkinson’s Disease Patients

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