Indian Parkinson's Disease Patients Research Articles

Social Cognition in Parkinson's Disease: A Case-Control Study.

Social cognition is the study of how people make sense of themselves and others. Impairment in several domains of social cognition is increasingly being recognized in Parkinson's disease (PD). We aimed to study multiple domains of social cognition in Indian PD patients using a culturally appropriate, validated instrument. We recruited 52 individuals with PD and 31 healthy volunteers (HV) and used the Social Cognition Rating Tools in Indian Setting (SOCRATIS) tool to assess theory of mind (ToM), attributional biases and social cue perception. Quality of life (QoL) was assessed using the PDQOL scale. Baseline characteristics were comparable between PD and HV. The mean (SD) FOT index (first order ToM index) was 0.86(0.18) in PD and 0.99(0.07) in HV [P < 0.001]. The PD group showed higher Externalizing Bias [EB, 4.42(3.91)], compared to HV [1.58(3.22), P=0.001]. The mean (SD) Faux Pas Composite Index (FPCI ALT) was 0.69(0.09) in PD and 0.78(0.13) in HV [P < 0.001]. Social cognition indices were not associated with QoL in PD. Clinical parameters-age, gender, HAM-D, MOCA, education, levodopa equivalent daily dose of medication, number of PD drugs and trihexyphenidyl use did not predict social cognition. PD patients were less successful than age, gender matched controls in understanding social situations and other's thought processes and had higher tendency to attribute undesirable events to external causes. Deficits in social cognition did not impair the quality of life.

Neurogenic Supine Hypertension and Cardiovascular Autonomic Dysfunction in Patients with Parkinson's Disease.

Natural history and disease progression in patients with Idiopathic Parkinson's Disease (PD) is quite heterogeneous. Autonomic dysfunction occurs commonly among Idiopathic PD patients. Heart rate variability and ambulatory blood pressure monitoring are used to assess cardiac autonomic dysfunction. The prevalence and magnitude of supine hypertension in Indian PD patients has not been studied to date. The present study aimed to record cardiovascular autonomic functions and supine hypertension in PD patients and to correlate them with the age of onset, duration and severity of the disease, and non-motor symptom burden. The cross-sectional study involved 60 PD patients. Webster rating scale was used to determine the disease severity. Non-motor symptom burden was assessed using the Non-Motor Symptom Scale (NMSS). Ambulatory blood pressure monitoring and heart rate variability parameters determined cardiac autonomic function. Supine hypertension was defined as Systolic Blood Pressure (SBP) ≥150 mmHg and/or DBP ≥90 mmHg. Less than 10% decrease or even increase in blood pressure during the night were classified as non-dippers. Pearson coefficient was used appropriately to establish correlation. P ≤ 0.05 was considered significant. Age of onset was 61.2 ± 8.7 years and duration of disease was 1.7 ± 1.1 years. Mean Webster and non-motor symptom scores were 12.7 ± 4.4 and 15.5 ± 8.0, respectively. About 50 patients (83%) were non-dipper, while 32 (53%) had supine hypertension. Low Frequency oscillations (LF) (r = 0.28), High Frequency oscillations (HF) (r = 0.29), Standard Deviation NN intervals (SDNN) (0.26), and Root Mean Squared Successive Differences of NN intervals (RMSSD) (r = 0.28) correlated significantly with non-motor symptoms scale. LF (r = -0.39), HF (r = -0.43), SDNN (-0.40), RMSSD (r = -0.41), NN50 (r = -0.38), PNN50 (r = -0.42), mean SBP (r = 0.26), and mean DBP (r = 0.33) correlated significantly with disease duration. PNN50 (r = -0.255), mean SBP (r = -0.29), and mean DBP (r = -0.27) correlated significantly with age at onset. Awareness regarding neurogenic supine hypertension is needed as it occurs commonly among Indian PD patients. Heart rate variability (HRV) parameters and ambulatory blood pressure are of significant help in the detection of early cardiovascular autonomic dysfunction and correlate significantly with disease duration and non-motor symptom burden among PD patients.

Translation of Parkinson's Disease Sleep Scale-2 (PDSS-2) in Hindi (H-PDSS-2) and its Validation for Assessment of Sleep Disturbances among Indian Parkinson's Disease Patients

Translation of Parkinson's Disease Sleep Scale-2 (PDSS-2) in Hindi (H-PDSS-2) and its Validation for Assessment of Sleep Disturbances among Indian Parkinson's Disease Patients

Loss of GSK-3β mediated phosphorylation in HtrA2 contributes to uncontrolled cell death with Parkinsonian phenotype

HtrA2, a proapoptotic mitochondrial serine protease, promotes cellular protection against oxidative damage. Literature reports show positive correlation between loss of HtrA2 protease activity and Parkinson's Disease (PD) susceptibility. Homozygous loss-of-function mutations in murine-HtrA2, and when they rarely occur in humans result in severe neurodegeneration and infantile death. Here, we report a novel heterozygous pathogenic HTRA2 variant, c.725C > T (p.T242M) in Indian PD patients. Although, this mutation exhibits no significant conformational changes compared to the wild-type, functional studies with HtrA2-T242M transfected neurons reveal common features of PD pathogenesis such as dysfunction, altered morphology and mitochondrial membrane depolarization. Despite exhibiting two-fold decrease in enzyme activity, observation of excessive cell-death due to over-expression of the mutant has been correlated with it being constitutively active. This interesting behavioral anomaly has been attributed to the loss of phosphorylation-mediated regulatory checkpoint at the T242M mutation site that is otherwise controlled by glycogen synthase kinase-3β (GSK-3β). This study, with seamless amalgamation of biophysical and biomedical research unravels a mechanistic pathway of HtrA2 regulation and delineates its biological role in PD. Therefore, this investigation will not only prove beneficial toward devising therapeutic strategies against HtrA2-associated diseases mediated by GSK-3β but also suggest new avenues for treatment of Parkinsonian phenotype.

Enhancing Quality of Life in Indian Parkinson's Disease Patients with Improved Measurement of Psychological Domains: A Perspective.

Parkinson's disease (PD) is the second most common progressive neuro-degenerative disorder. Research in PD is gradually increasing in India due to increased clinical cases, which could double by 2030 worldwide. Although its prevalence is low in India as compared to other countries, the total burden is much higher due to the large population size. PD is progressively debilitating, with pronounced motor and nonmotor symptoms (NMSs) that severely affect the quality of life (QoL) of patients and their caregivers. The progressive nature of the disease lays great emphasis on doctors to focus on the patients’ QoL. As a consequence, Health-related QoL (HRQoL) has gradually become one of the main indicators for assessing health-related outcome. There is a growing need to pay attention to the NMSs and a pressing need to look at the QoL of Indian patients with PD through a culture and value specific lens. Research into the holistic QoL assessment with emphasis on psychological domains may allow for the early evaluation and intervention of depressive and cognitive symptoms in PD. This could result into increased productivity, reduced morbidity, and healthcare cost, which would in turn result into better QoL of Indian PD patients.

Genetic Architecture of Parkinson's Disease in the Indian Population: Harnessing Genetic Diversity to Address Critical Gaps in Parkinson's Disease Research.

Over the past two decades, our understanding of Parkinson's disease (PD) has been gleaned from the discoveries made in familial and/or sporadic forms of PD in the Caucasian population. The transferability and the clinical utility of genetic discoveries to other ethnically diverse populations are unknown. The Indian population has been under-represented in PD research. The Genetic Architecture of PD in India (GAP-India) project aims to develop one of the largest clinical/genomic bio-bank for PD in India. Specifically, GAP-India project aims to: (1) develop a pan-Indian deeply phenotyped clinical repository of Indian PD patients; (2) perform whole-genome sequencing in 500 PD samples to catalog Indian genetic variability and to develop an Indian PD map for the scientific community; (3) perform a genome-wide association study to identify novel loci for PD and (4) develop a user-friendly web-portal to disseminate results for the scientific community. Our “hub-spoke” model follows an integrative approach to develop a pan-Indian outreach to develop a comprehensive cohort for PD research in India. The alignment of standard operating procedures for recruiting patients and collecting biospecimens with international standards ensures harmonization of data/bio-specimen collection at the beginning and also ensures stringent quality control parameters for sample processing. Data sharing and protection policies follow the guidelines established by local and national authorities.We are currently in the recruitment phase targeting recruitment of 10,200 PD patients and 10,200 healthy volunteers by the end of 2020. GAP-India project after its completion will fill a critical gap that exists in PD research and will contribute a comprehensive genetic catalog of the Indian PD population to identify novel targets for PD.

Pain Assessment in Indian Parkinson's Disease Patients Using King's Parkinson's Disease Pain Scale.

Background:Pain is a common symptom in Parkinson's disease (PD) patients. Scales to rate pain in PD are marred by several flaws, either not being available in other languages or not specific for PD.Objectives:To assess the frequency of pain among bilingual Indian PD patients using “King's Parkinson's disease pain scale” (KPPS) and to validate it.Methods:We randomly administered KPPS in Hindi/English to all consecutive bilingual persons with PD. The results were appropriately analyzed.Results:A total of 119 PD patients were enrolled with a mean age of 64.34 (± 9.57) years. Median Hoehn and Yahr stage was 2 (42.85%). Pain was present in 62 (52.1%) PD patients. The most common type was musculoskeletal (74.19%). The mean total KPPS score was 16.02 ± 10.57. KPPS score was significantly higher in women and correlated positively with unified Parkinson's disease rating scale (UPDRS) part 2 and 4 scores (r = 0.27 and r = 0.25). Risk factors for pain were female gender, higher H and Y stage, total UPDRS score, and individual UPDRS part 3 and 4 scores. Difficulty falling asleep (P = 0.01), frequent awakenings (P = 0.01), diminished smell sensation (P = 0.003), diminished speech volume (P = 0.02), gait freezing (P = 0.03), and falls (P = 0.001) correlated with the presence of pain. The interclass correlation coefficient between the Hindi and English versions of KPPS was 0.835, while Bland–Altman analysis showed 96.7% agreement suggesting excellent correlation and validation.Conclusions:KPPS is an easy tool for characterization, scoring, and follow-up of pain in PD patients. The Hindi version has good agreement with the original English version.

Serum B12, homocysteine levels, and their effect on peripheral neuropathy in Parkinson's disease: Indian cohort

Background:Cobalamin deficiency, either due to dietary inadequacy or increased consumption attributable to levodopa-mediated metabolic disturbance, and resultant hyperhomocysteinemia may contribute to peripheral neuropathy (PN) in Parkinson's disease (PD).Aim:The aim of the study is to assess the prevalence of Vitamin B12 deficiency, hyperhomocysteinemia in Indian PD patients, and their association with PN.Materials and Methods:Clinical details were collected in 93 patients over a period of 2 years. Seventy controls were included in the study. Serum B12, homocysteine, folate, electroneurography, and autonomic function tests were done. The prevalence of B12 deficiency and hyperhomocysteinemia in PD patients and controls was assessed. The association of B12 and homocysteine levels with patients’ age, disease duration, levodopa equivalent daily dose, cumulative levodopa dose, Unified Parkinson's Disease Rating Scale-III off score, modified Hoehn and Yahr score, and presence or absence of PN was studied.Results:Serum B12, homocysteine levels, prevalence of B12 deficiency, and hyperhomocysteinemia were no different between cases and controls. Seven of 93 (9.68%) PD patients had PN. The median values of serum B12, folate, and homocysteine levels across patients with or without PN could not be compared as only seven of our patients had PN.Conclusion:The prevalence of B12 deficiency, hyperhomocysteinemia, and incidence of PN among our patients is very less when compared to the Western population. The conjecture that PN in PD patients may be secondary to B12 deficiency/hyperhomocysteinemia stands as a speculation.

Role of Apolipoprotein E, Cathepsin D, and Brain-Derived Neurotrophic Factor in Parkinson's Disease: A Study from Eastern India.

Parkinson's disease (PD) is a progressive neurodegenerative disease with complex etiology. Both genetic and environmental factors play significant role. Apart from candidate genes, some modifier genes have been reported to be associated with the altered risk of PD. Previous studies have identified Apolipoprotein E (APOE), Cathepsin D (CTSD), and Brain-Derived Neurotrophic Factor (BDNF) as key players of neurodegenerative pathways with their variants associated with different neurodegenerative diseases. Hence, this study aims to identify the potential role of these modifier genes in the pathogenesis of PD among Eastern Indian PD patients. A case-control study was performed using 302 clinically diagnosed PD patients and 304 ethnically matched controls. Promoter SNPs of APOE (rs449647, rs405509) and BDNF (rs56164415), and coding SNPs of APOE (rs429358, rs7412 resulting in ε2, ε3, and ε4 alleles), CTSD (rs17571), and BDNF (rs6265) were analyzed by PCR-RFLP and bidirectional sequencing. The effect of rs56164415 on BDNF expression was characterized by Luciferase assay. APOEε4 allele was significantly overrepresented (p value = 0.0003) among PD patients, whereas ε3 allele was predominant in the control population. The promoter haplotype (A-rs449647, G-rs405509) of APOE was preponderant among female PD patients posing risk. No association was found for CTSD polymorphism. The 'T/T' genotype of BDNF rs56164415 was overrepresented (p-value = 0.02) among early onset PD patients. Expression of BDNF for the 'T/T' variant was significantly lower (p-value = 0.012) than the 'C/C' variant, suggesting a possible role in PD pathogenesis. This study suggests that APOE and BDNF may serve as modifier loci among eastern Indian PD patients.

Association of Helicobacter pylori with Parkinson's Disease.

Background and PurposeParkinson's disease (PD) is a major neurological disorder that requires lifelong treatment, and the combined presence of Helicobacter pylori (H. pylori) infection can increase the required anti-PD medications. We aim to investigate the effect of H. pylori infection in Indian PD patients.MethodsWe prospectively recruited 36 PD patients from December 2007 to January 2011. All patients underwent a detailed neurological evaluation and serological examination for H. pylori infection. Seropositive and seronegative patients were considered to be the cases and controls, respectively. All patients who were seropositive received triple therapy for 2 weeks. Outcome measures of the mean ‘off’ Unified Parkinson's Disease Rating Scale (UPDRS)-III score, mean ‘on’ UPDRS-III score, mean onset time, mean ‘on’ duration, and mean daily ‘on’ time were measured at baseline and at a 3-week follow-up.ResultsH. pylori-IgG positivity was present in 18 (50%) PD patients. The prevalence of men (72.2% vs. 33.3%), mean duration of disease (13.8 vs. 12.5) and mean levodopa equivalent daily dose (824 mg vs. 707 mg) were significantly higher among H. pylori positive patients than in controls (p<0.0001). Controls had a significantly longer ‘on’ duration and daily ‘on’ time, and better ‘on’ UPDRS-III scores. Seropositive patients took a significantly longer time to turn ‘on’ after a levodopa challenge. At the 3-week follow-up, H. pylori eradication significantly improved the mean ‘on’ UPDRS-III score, onset time, ‘on’ duration, and daily ‘on’ time.ConclusionsH. pylori infection was present in 50% of Indian PD patients. H. pylori seropositivity was associated with a poor response to levodopa and increased medication usage, while eradication therapy was associated with better patient outcomes.

Complementary and alternative medicine in Indian Parkinson's disease patients

Use of complementary and alternative medicine (CAM; 補充與替代醫學 bǔ chōng yǔ tì dài yī xué) in Parkinson disease (PD) ranged 40–70%. The objective of this study was to determine the frequency, types and factors associated with the use of CAM in Indian PD patients. PD patients, fulfilling UKPD-Society brain-bank diagnostic-criteria, attending Movement-disorders clinic of a tertiary-care teaching hospital in India from 1st May to 15th December 2012 were enrolled. Information on socio-demographic, clinical data and treatment along with factors (source of information, benefits, harms, reason for use and cost) associated with CAM use were recorded. Out of 233 consecutive PD patients, 106 (46%) used CAM. Mean ± SD age of CAM users was 56 ± 11.2 years. Among CAM users, 72% were males, with mean age-onset 49 ± 11.16 years (P = 0.042) and 73% receiving levodopa therapy (p = 0.006). Longer duration PD, higher education (graduates and above), urban residence, and fairly good perceived health were other factors seen among CAM users. Reasons for using CAM were ‘feel good factor’ (73%), 9% took CAM due to side effects from allopathic-medicines. Commonly used CAM were Ayurvedic, homeopathic medicines, and acupuncture (針灸 zhēn jiǔ) [74/106 (70%)]. Median CAM cost in Indian Rupees (INR) was 1000/month (USD16, range: 0-400USD/month in year 2012). Almost half of PD patients use CAM. Three-quarters of Indian CAM using PD patients believe that CAM is harmless, using it at a substantial cost. CAM-users are educated, young, urban dwellers, longer duration PD and receiving levodopa. Commonly used CAM was Ayurvedic, Homeopathic medicines and acupuncture.

Non-motor symptoms in an Indian cohort of Parkinson's disease patients and correlation of progression of non-motor symptoms with motor worsening.

To document the frequency and prevalence of non-motor symptoms (NMS) in an Indian cohort of Parkinson's disease (PD) patients. To validate the non-motor score scale (NMSS) in an Indian cohort of PD patients for recording NMS of the disease, to study the prevalence and frequency of NMS in Indian PD patients using the NMSS, and to compare the progression of NMS with motor worsening. Conclusion and Results: This was a cross-sectional, single-center, open-label, one point in time evaluation study conducted from 2009 to 2011. It validated the NMSS scale in an Indian population. The study has profiled the prevalence and pattern of NMS in an Indian cohort of PD patients. Comparison of NMS scale scores with the Unified PD Rating Scale motor scores demonstrated a correlation between non-motor and motor symptoms in the disease progression, particularly of manifestations related to the cognitive decline, memory disturbances, urinary incontinence and smell.

Impulse control disorders and related behaviours (ICD-RBs) in Parkinson's disease patients: Assessment using "Questionnaire for impulsive-compulsive disorders in Parkinson's disease" (QUIP).

Background:There is limited data on the prevalence of impulse control disorder and related behaviors (ICD-RBs) in Indian patients with Parkinson's Disease (PD). In the context of potential genetic and environmental factors affecting the expression of ICD-RBs, studying other multiethnic populations may bring in-sights into the mechanisms of these disorders.Objectives:To ascertain point prevalence estimate of ICD-RBs in Indian PD patients, using the validated “Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease (QUIP)” and to examine their association with Dopamine replacement therapy (DRT).Materials and Methods:This was a hospital based observational cross-sectional study. After taking informed consent, patients and their informants (spouse, or primary caregiver) were made to complete the QUIP, and were instructed to answer questions based on behaviors that occurred anytime during PD that lasted at least four consecutive weeks.Results:Total of 299 patients participated in the study. At least one ICD-RB was present in 128 (42.8%), at least one Impulse control disorder (ICD) was present in 74 (24.75%) and at least one Impulse control related compulsive behaviour (ICRB) was present in 93 (31.1%) patients. Punding was the most frequent (12.4%) followed by hyper sexuality (11.04%), compulsive hobbyism (9.4%), compulsive shopping (8.4%), compulsive medication use (7.7%), compulsive eating (5.35%), walkabout (4%) and pathological gambling (3.3%). ≥ 2 ICD-RBs were observed in 15.7% of patients. After multivariate analysis, younger age of onset, being unmarried were specifically associated with presence of ICD. Longer disease duration was specifically associated with presence of ICRB. Whereas smoking and higher dopamine levodopa equivalent daily doses (DA LEDD) were associated with both presence of ICD and ICRB. Higher LD LEDD was specifically associated with presence of ICD-RB.Conclusions:Our study revealed a relatively higher frequency of ICD-RBs, probably because of the use of screening instrument and because we combined both ICDs and ICRBs. Also high proportion of DA use (81.6%) among our patients might be responsible. The role of genetic factors that might increase the risk of developing ICD-RBs in this population needs further exploration.

Altered oxidative stress levels in Indian Parkinson's disease patients with PARK2 mutations.

The aim of this pilot study was to determine the baseline state of oxidative stress indices in patients with Parkinson's disease (PD). Peripheral blood samples of 15 PD subjects were analyzed and compared with ten age matched healthy controls. Patients with PARK2 mutations were also compared with PD patients without mutations. There was significant increase in malondialdehyde content and superoxide-dismutase (SOD) activity in peripheral blood parameters in PD patients (p < 0.05) in comparison to controls. These findings suggest an important role of oxidative stress in Parkinson's disease evolution and progress. No changes were observed in glutathione peroxidase and nitric oxide levels. We found significant correlation between SOD activity and lipid peroxidation when the biochemical data was further analyzed. In addition, significant increase in the levels of SOD among the PD patients with PARK2 mutations was observed, which can be ascribed to chronic oxidative stress induced by PARK2 mutations.

Evaluating intra-genetic variants of DJ-1 among Parkinson's disease patients of Eastern India

Objectives: Mutations in the DJ-1 gene have been described in autosomal recessive Parkinson's disease (PD) of European ancestry, Ashkenazi Jews, and Afro-Caribbean patients. Up to date, there is a lack of information about the prevalence of DJ-1 mutations among Indian PD patients.Materials and methods: In this study, we examined for DJ-1 mutations in Eastern Indian PD patients. Exons (no. 2-7) and intron boundaries of the DJ-1 gene were screened in 300 individuals (PD, 150; controls, 150) by direct sequencing.Results: A total of six intronic variants (IVS4+30T>G, IVS4+45G>A, IVS4+46G>A, IVS4-98G>A, IVS5+31G>A and IVS5+69G>C) were detected including one novel intronic change (IVS5+69G>C). Clinical features of the two patients exhibiting IVS5+69G>C (novel change) were compared and both were found to have early onset PD. IVS4+30T>G, IVS4+45G>A, and IVS4+46G>A were found to be present equally both in the patient and control cohorts. We did not find any DJ-1 mutations in our study.Conclusion: Our results suggest that, unlike Parkin, pathogenic DJ-1 mutations seem to be restricted in certain populations and are unlikely to be of clinical importance in the eastern part of India.

Absence of Commonly Reported Leucine-Rich Repeat Kinase 2 Mutations in Eastern Indian Parkinson's Disease Patients

Pathogenic mutations in leucine-rich repeat kinase 2 (LRRK2; PARK8) encoding dardarin, implicated in patients with autosomal dominant and sporadic Parkinson's disease (PD) among different ethnic groups (Ashkenazi Jews, North African Arabs, Basques) might be of some help in diagnostic screening and genetic counseling. We investigated the seven common mutations spanning exons 31, 35, and 41 reported in the LRRK2 gene among Eastern Indian patients with PD. Mutations R1441G, R1441C, R1441H, G2019S, Y1699C, I2020T, and I2012T were screened in 320 individuals (PD, 150 and controls, 170) by direct sequencing. We did not observe any of these abovementioned mutations in our studied individuals. We conclude that these mutations are rare causes of PD in the Eastern Indian population and, therefore, of little help for genetic counseling and diagnostic purposes.

Evaluation of PINK1 variants in Indian Parkinson's disease patients

Mutations in PINK1 have been identified in familial and sporadic cases of early onset Parkinson's disease (PD). To determine the contribution of PINK1 variants in Indian PD patients, the gene was screened in 250 patients and 205 ethnically matched controls by polymerase chain reaction, single-stranded conformation polymorphism and DNA sequencing. Two potentially pathogenic variants (Arg246Gln & Arg276Gln) were detected in the heterozygous state in 5 patients; none of the patients carried homozygous or compound heterozygous mutations. In addition, 13 other variants were identified, including a known polymorphism (Ala340Thr), a few synonymous or intronic changes, none of which are likely to be pathogenic. Unlike the Chinese population, the Ala340Thr variant did not show any association with PD in Indian population. Six single nucleotide polymorphisms (SNPs) selected from dbSNP were genotyped in 531 normal, healthy individuals representing different ethnic groups of India. Most of the SNP markers were observed to be highly heterozygous among Indians, which could be used for segregation analysis of PINK1 alleles in familial PD cases.

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

BackgroundAmong several aetiological factors, PARK2 mutations are the most common cause of Parkinson disease (PD) that result in degeneration of dopaminergic neurons in the substantia nigra.MethodsIn order to examine the...

Absence/rarity of commonly reported LRRK2 mutations in Indian Parkinson's disease patients

Recent discovery of pathogenic mutations in the leucine-rich repeat kinase 2 (LRRK2) gene in Parkinson's disease (PD) patients in different ethnic groups have raised a hope of diagnostic screening and genetic counseling. We investigated the six most commonly reported mutations in LRRK2 gene among Indian PD patients, using PCR-RFLP method. Mutations G2019S, R1441C, R1441G, and R1441H were screened in 1012 individuals (PD, 800; controls, 212) while mutations I2012T and I2020T were screened in 748 PD patients. We did not observe any of these six mutations in this study sample except in a single female young onset PD patient who showed a heterozygous G2019S mutation. The absence of mutations was reconfirmed by sequencing of probands from several autosomal dominant PD families. Our observations suggest that these mutations may be a rare cause of PD among Indians and therefore of little help for diagnostic screening and genetic counseling for Indian PD patients.

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

Parkinson's disease (PD), the second most common neurodegenerative disorder, affects at least 1% of the population over the age of 50. However, very little information is available regarding the molecular basis of PD among Indians. Since the largest number of mutations have been detected in the Parkin gene among all known PD loci, we aim to use Parkin as the candidate gene to assess its role in PD-related pathogenesis in Indian patients. A total of 138 PD patients, with the mean age of onset being 47±14 (age range, 5–77 years), and 100 controls were recruited for the study from eastern India. Parkin mutations were detected by amplification of exons of the gene along with the flanking splice junctions by polymerase chain reaction, single-stranded conformation polymorphism and DNA sequencing. A total of 18 nucleotide variants including six novel changes were detected. These include five missense mutations (Gln34Arg, Arg42Cys, Arg42His, Tyr143Cys and Arg334Cys) detected in eight patients in heterozygous condition and a homozygous deletion encompassing exons 3 and 4 in two sibs affected with PD. Clinical features of the Parkin mutants were compared. Among eastern Indian PD patients, mutation in Parkin was identified in 7.24% cases.