Parkin mutations in familial and sporadic Parkinson's disease among Indians

Chaudhary, Shashi; Behari, Madhuri; Dihana, Maninder; Swaminath, Pazhayannur V.; Govindappa, Shyla T.; Jayaram, Sachi; Goyal, Vinay; Maitra, Arindam; Muthane, Uday B.; Juyal, Ramesh C.; Thelma, B.K.

doi:10.1016/j.parkreldis.2005.12.004

Cited by 46 publications

(36 citation statements)

References 34 publications

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“…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. First, selection bias in the study might have affected our results, although the genotype distribution of patients and controls in our study was compatible with the Hardy-Weinberg expectations.…”

Section: Discussionmentioning

confidence: 93%

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: Discussionmentioning

confidence: 93%

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

et al. 2015

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“…This analysis resulted after multiple comparisons of socio-economic and demographic characteristics of the 1,010 randomly sampled patients with the background population, which was found to be comparable. It is speculated that the higher occurrence of PARK2 mutations [14,15] could be due to the higher proportion of never-smokers in this region. Almost 15% of the randomly sampled 1,010 patients were found to be smokers, which is comparable to previous reports [16] .…”

Section: Discussionmentioning

confidence: 99%

Occurrence of <i>PARK2</i> Mutations in a Never-Smoker Population with Parkinson’s Disease in North India

Prabhakar

Vinish²,

Das³

et al. 2010

Neuroepidemiology

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Background: Parkinson’s disease (PD) is a complex neurological disorder without any well-documented genotype-demography associations among sporadic variants. We recently reported PARK2 mutations to be constituting 40% of PD in this region and thus analysed how demographic variables associate with PARK2 mutations in 70 of these patients. Methods: PD samples were screened by PCR single-strand conformation polymorphism (SSCP) and sequencing and their demographic data collected. Demographic and religion data was obtained from 1,010 randomly selected individuals of 120,000 patients visiting the Neurology Clinic and was compared with state database and PD patients. Results: Sikhs from a rural background exhibited the majority of PARK2 mutations. The frequency of PARK2 mutations among females was significantly higher as compared to males (p < 0.015). The age of onset of PD patients with a rural background was found to be significantly lower as compared to patients with an urban background (p < 0.004). The demographic spectrum of the 1,010 randomly selected patients and the background population was found to be comparable. Conclusions: As PD patients with PARK2 mutations were found to be of sporadic origin and never-smokers, a non-redundant inverse relationship between founder PARK2 mutations and smoking is implicated to account for its high frequency. The predisposition of Sikhs to PARK2 mutations necessitates a larger study among its familial variants and a control smoker PD population. The spectrum of PARK2 mutations among Sikh smokers is difficult to study because of the religion-based aversion to smoking.

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“…For this reason, more than 200 putative pathogenic mutations have been reported worldwide, affecting numerous ethnic populations [33,35,59,[64][65][66][67][68][69][70][71][72][73][74][75][76][77]. The PARK2 mutation spectrum includes homozygous or compound heterozygous missense and nonsense point mutations, as well as several exon rearrangements (both duplications and deletions) involving all 12 exons and the promoter region.…”

Section: Park2mentioning

confidence: 99%

Genetics of Parkinson’s Disease: The Role of Copy Number Variations

Cognata¹,

D’Agata²,

Cavalcanti³

et al. 2016

Challenges in Parkinson's Disease

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Parkinson's disease (PD), the second most common progressive neurodegenerative disorder, was long believed to be a non-genetic sporadic origin syndrome. The identification of distinct genetic loci responsible for rare Mendelian forms of PD has represented a revolutionary breakthrough, allowing to discover novel mechanisms underlying this debilitating still incurable condition. Along with single-nucleotide polymorphisms (SNPs), other kinds of DNA molecular defects have emerged as significant disease-causing mutations, including large chromosomic structural rearrangements and copy number variations (CNVs). Due to their size variability and to the different sensitivity and resolution of detection methodologies, CNVs constitute a particular challenge in genetic studies and the pathogenetic or susceptibility impact of specific CNVs on PD is currently under debate. In this chapter, we will review the current literature and bioinformatic data describing the involvement of CNVs on PD pathobiology. We will discuss the recently highlighted role of PARK2 heterozygous CNVs, the possible common founder effects of PD gene rearrangements and the importance to map genetic breakpoints. We will also add a summary about the current available molecular methods and bioinformatics web resources to detect and interpret CNVs. Assessing the global genome-wide burden of large CNVs and elucidating the role of de novo rare structural variants on PD may reveal new candidate genes and consequently ameliorate diagnosis and counselling of mutations carriers.

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Parkin mutations in familial and sporadic Parkinson's disease among Indians

Cited by 46 publications

References 34 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

Occurrence of <i>PARK2</i> Mutations in a Never-Smoker Population with Parkinson’s Disease in North India

Genetics of Parkinson’s Disease: The Role of Copy Number Variations

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