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Journal ArticleDOI

Movement disorders: Indian scenario: a clinico-genetic review.

01 Sep 2013-Neurology India (Medknow Publications)-Vol. 61, Iss: 5, pp 457-466

TL;DR: Common problems of MDs in India with regard to epidemiology, clinical features and genetics are highlighted.

AbstractMovement 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.

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Citations
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Journal ArticleDOI
TL;DR: The core neuroanatomical features of resilience against PD and evidence for ethnicity-based differential prevalence are presented and similar neural correlates of resilience are envisaged in the Anglo-Indian population.
Abstract: Disease genetics in admixed populations like Hispanic-Americans, African-Americans, etc. are gaining importance due to high disease burden in them. Furthermore, epidemiological studies conclusively prove ethnicity-based differential prevalence of Parkinson's disease (PD), since the American-Caucasians are more susceptible than Asian-Indians and Africans. Contradictorily, Anglo-Indians, an admixture of Europeans and Asian-Indians are five-times less susceptible than Indians. We evaluated the neural basis of this phenomenon using the cytomorphological features of susceptibility to nigrostriatal neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The nigral dopaminergic neuronal numbers, their size and tyrosine hydroxylase (TH), PitX3 and Nurr1 expression were compared in MPTP-susceptible C57BL/6J mice, MPTP-resistant CD-1 mice and their crossbreds using stereology, morphometry and densitometry. Apoptotic index was evaluated by TUNEL-assay and caspase-3 expression. Striatal volume, TH and glial derived neurotrophic factor (GDNF) expression were studied. The normal CD-1 and crossbreds had significantly more, although smaller, nigral dopaminergic neurons than C57BL/6J, and a larger striatum. The crossbreds had higher TH, Nurr1 and PitX3 levels. MPTP administration caused loss of ~50-60 % nigral dopaminergic neurons in C57BL/6J and ~15 % in CD-1, but none in crossbreds. MPTP-induced cellular shrinkage in C57BL/6J was contrasted by nuclear enlargement without somal alterations in resistant strains. MPTP lowered the striatal TH and GDNF in C57BL/6J. Elevated striatal GDNF in CD-1 and crossbreds could be of compensatory nature and complemented the reduced nigral caspase-3 expression to attenuate and/or block apoptosis. Similar neural correlates of resilience are envisaged in the Anglo-Indian population. Thus, we present the core neuroanatomical features of resilience against PD and evidence for ethnicity-based differential prevalence.

18 citations


Cites background from "Movement disorders: Indian scenario..."

  • ...However, in the Asian-Indian population, studies report absence of mutations in SNCA/α-synuclein gene while mutations in DJ-1, PINK1 and LRRK2 genes are rare [39, 40]; hence, we did not choose a genetic model of the disease....

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Journal ArticleDOI
TL;DR: Genetic variability in LRRK2 has been unequivocally established as a major risk factor for familial and sporadic forms of PD in ethnically diverse populations.
Abstract: BACKGROUND Genetic variability in LRRK2 has been unequivocally established as a major risk factor for familial and sporadic forms of PD in ethnically diverse populations. OBJECTIVES To resolve the role of LRRK2 in the Indian population. METHODS We performed targeted resequencing of the LRRK2 locus in 288 cases and 298 controls and resolved the haplotypic structure of LRRK2 in a combined cohort of 800 cases and 402 controls in the Indian population. We assessed the frequency of novel missense variants in the white and East Asian population by leveraging exome sequencing and densely genotype data, respectively. We did computational modeling and biochemical approach to infer the potential role of novel variants impacting the LRRK2 protein function. Finally, we assessed the phosphorylation activity of identified novel coding variants in the LRRK2 gene. RESULTS We identified four novel missense variants with frequency ranging from 0.0008% to 0.002% specific for the Indian population, encompassing armadillo and kinase domains of the LRRK2 protein. A common genetic variability within LRRK2 may contribute to increased risk, but it was nonsignificant after correcting for multiple testing, because of small cohort size. The computational modeling showed destabilizing effect on the LRRK2 function. In comparison to the wild-type, the kinase domain variant showed 4-fold increase in the kinase activity. CONCLUSIONS Our study, for the first time, identified novel missense variants for LRRK2, specific for the Indian population, and showed that a novel missense variant in the kinase domain modifies kinase activity in vitro. © 2018 International Parkinson and Movement Disorder Society.

7 citations


Cites background from "Movement disorders: Indian scenario..."

  • ..., G2019S) primarily identified in the white population—and excluded the role of these LRRK2 variants in the Indian PD population.(23,25,50,51) Here, we performed the first comprehensive study using targeted sequencing in Indian PD patients, which led to the identification of populationspecific novel variants and underscores the relevance of allelic heterogeneity in PD....

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Journal ArticleDOI
TL;DR: The relevance, importance, and translational impediments of contemporary advances to implement public health principles into practice has neither been attempted nor impacted on disease burden or the authors' preparedness to prevent eventualities.
Abstract: It is now recognized worldwide that anticipation and prevention of diseases have significant advantages for the health and healthy ageing of the population. Early recognition of the disease in a vulnerable population such as in children aged 60 years enhances our preparedness for any eventualities and future burden of the diseases to society. It is also recognized that current public health practices alone cannot bring about the desired outcome. When tackling public health-related issues, such problems must be recognized and state-of-the-art principles and innovations from genomic sciences, information technologies, and medical specialties must be encompassed and embraced. These will enhance strategies for preparedness and provide us with a better understanding of how to identify, manage, and control disease burdens. The ever expanding landscape of genomics research also includes experimental and computational approaches for effectively utilizing DNA sequence information. From these perspectives, the intricacies of Mendelian single gene disorders are the least challenging compared to intricacies of multi-dimensional host factors for infectious diseases or complex disorders such as cancer. The concepts of public health in India are on firm footing; however, integration of contemporary advances to implement public health principles into practice has neither been attempted nor impacted on disease burden or our preparedness to prevent eventualities. At the same time, translational genomics is gradually paving the way for personalized medicine. Principles of personalized medicine remain to be fully understood and practiced despite the pharmacogenomics-based future of drug development, and treatment has not been as exciting as the advances in genomics we are witnessing today. The relevance, importance, and translational impediments of these advances will be discussed.

6 citations

Journal ArticleDOI
01 Jan 2019
Abstract: Movement Disorders are currently growing to be one of the major subspecialties of neurology worldwide, primarily by developments of research and therapeutics in this field. As any specialty grows, it leads to the formation of its society and the publication of journal to disseminate the knowledge. The International Parkinson’s Disease and Movement Disorders Society (IPMDS, formerly known as Movement Disorders Society) played its role with inception since 1980s. Further development of Movement Disorders subspecialty leads each region and country to have their own national societies and publications. Similarly, the seeds of Movement Disorders were sown in India in mid-1980s but it took a major stride in last few years with the formation of Movement Disorders Society of India (MDSI) in 2014 and following this, it is now at the crux of starting its journal—Annals of Movement Disorders (AOMD). This would be a right time to look back into the history of Indian Neurology with specific reference to the Movement Disorders and pen down these chronicles since the inception of modern neurology in India. The current chronicles of Indian Movement Disorders is penned based on personal interviews with various senior Movement Disorder specialists of India. However, it should also be remembered that many of the chronicles are limited by the memories of people and their biases with whom the interviews are conducted.

3 citations


Cites background from "Movement disorders: Indian scenario..."

  • ...Das contributed on the epidemiology of various movement disorders.[18] The other important contribution of Indian literature has been on SCA-12....

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Journal ArticleDOI
S. Bashir Ahmad, Zahid Bashir, Tak S, Goyal, M Behari 
TL;DR: Familiarity showed that focal dystonia were more common even in younger age group with Writers cramp most common among all dySTONia followed by cervical dystonic followed by writer’s cramp.
Abstract: Objective: To study the demographic, clinical and etiological profile of dystonia in patients less than forty years of age. Material and Methods: In this study two hundred and nineteen patients with different dystonia were included. Data on demographic profile, clinical and etiological profile was recorded and statistical analysis was done by using descriptive analysis (frequency distribution). Results: Out of two hundred and nineteen patients, one hundred thirteen (51.7%) were <26 years of age of onset and one hundred six (48.4%) had >26 years of age of onset with mean age of onset 22.3 years, one hundred seventy six were males and forty four females. Mean duration of illness was 4.4 years. Frequency of different dystonia was focal dystonia 57.72%, multifocal 1.36%, segmental 10%, generalized 29.09%, hemidystonia 3.63% and paroxysmal kinesigenic dystonia 2.72%. Among focal dystoniaWriter’s cramp was most common (63%) followed by cervical dystonia (17.32%), and blepharospasm(7%). Among generalized dystonia Wilson’s disease was most common etiological factor in 31.25% cases. Primary generalized dystonia was seen in 17.2% cases. MRI was abnormal in all eight cases of hemidystonia. SPECT brain was abnormal in 1 out of four cases of paroxysmal kinesigenic dystonia. DYT1 was positive in four out of eleven patients of primary generalized dystonia. Conclusion: Present study showed that focal dystonia were more common even in younger age group with Writers cramp most common among all dystonia followed by cervical dystonia. In hemidystonia structural lesion should always be ruled out.

2 citations


Cites background from "Movement disorders: Indian scenario..."

  • ...Their median age was fourteen (2-53) years and nine were females....

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References
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Journal ArticleDOI
TL;DR: It is demonstrated that an unequivocal role for common genetic variants in the etiology of typical PD and population-specific genetic heterogeneity in this disease is suggested, and supporting evidence that common variation around LRRK2 modulates risk for PD is provided.
Abstract: We performed a genome-wide association study (GWAS) in 1,713 individuals of European ancestry with Parkinson's disease (PD) and 3,978 controls. After replication in 3,361 cases and 4,573 controls, we observed two strong association signals, one in the gene encoding a-synuclein (SNCA; rs2736990, OR = 1.23, P = 2.24 x 10(-16)) and another at the MAPT locus (rs393152, OR = 0.77, P = 1.95 x 10(-16)). We exchanged data with colleagues performing a GWAS in Japanese PD cases. Association to PD at SNCA was replicated in the Japanese GWAS1, confirming this as a major risk locus across populations. We replicated the effect of a new locus detected in the Japanese cohort (PARK16, rs823128, OR = 0.66, P = 7.29 x 10(-8)) and provide supporting evidence that common variation around LRRK2 modulates risk for PD (rs1491923, OR = 1.14, P = 1.55 x 10(-5)). These data demonstrate an unequivocal role for common genetic variants in the etiology of typical PD and suggest population-specific genetic heterogeneity in this disease.

1,633 citations


"Movement disorders: Indian scenario..." refers background in this paper

  • ...Recent genome wide association studies on Asian and Caucasian populations have identified a number of associated genes in PD including ethnicity specific susceptible genes.[68,69] Majority of the mutations in the...

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Journal ArticleDOI
TL;DR: The results identify two new PD susceptibility loci, show involvement of autosomal dominant parkinsonism loci in typical PD and suggest that population differences contribute to genetic heterogeneity in PD.
Abstract: To identify susceptibility variants for Parkinson's disease (PD), we performed a genome-wide association study (GWAS) and two replication studies in a total of 2,011 cases and 18,381 controls from Japan. We identified a new susceptibility locus on 1q32 (P = 1.52 x 10(-12)) and designated this as PARK16, and we also identified BST1 on 4p15 as a second new risk locus (P = 3.94 x 10(-9)). We also detected strong associations at SNCA on 4q22 (P = 7.35 x 10(-17)) and LRRK2 on 12q12 (P = 2.72 x 10(-8)), both of which are implicated in autosomal dominant forms of parkinsonism. By comparing results of a GWAS performed on individuals of European ancestry, we identified PARK16, SNCA and LRRK2 as shared risk loci for PD and BST1 and MAPT as loci showing population differences. Our results identify two new PD susceptibility loci, show involvement of autosomal dominant parkinsonism loci in typical PD and suggest that population differences contribute to genetic heterogeneity in PD.

1,116 citations


"Movement disorders: Indian scenario..." refers background in this paper

  • ...Recent genome wide association studies on Asian and Caucasian populations have identified a number of associated genes in PD including ethnicity specific susceptible genes.[68,69] Majority of the mutations in the...

    [...]

Journal ArticleDOI
TL;DR: Genome-wide associations and re-sequencing projects, together with gene-environment interaction studies, are expected to further define the causal role of genetic determinants in the pathogenesis of PD, and improve prevention and treatment.
Abstract: Research in Parkinson's disease (PD) genetics has been extremely prolific over the past decade. More than 13 loci and 9 genes have been identified, but their implication in PD is not always certain. Point mutations, duplications and triplications in the alpha-synuclein (SNCA) gene cause a rare dominant form of PD in familial and sporadic cases. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are a more frequent cause of autosomal dominant PD, particularly in certain ethnic groups. Loss-of-function mutations in Parkin, PINK1, DJ-1 and ATP13A2 cause autosomal recessive parkinsonism with early-onset. Identification of other Mendelian forms of PD will be a main challenge for the next decade. In addition, susceptibility variants that contribute to PD have been identified in several populations, such as polymorphisms in the SNCA, LRRK2 genes and heterozygous mutations in the beta-glucocerebrosidase (GBA) gene. Genome-wide associations and re-sequencing projects, together with gene-environment interaction studies, are expected to further define the causal role of genetic determinants in the pathogenesis of PD, and improve prevention and treatment.

820 citations


"Movement disorders: Indian scenario..." refers background in this paper

  • ...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,[48‐52] PINK1,[53] DJ‐1,[54,55] and LRRK2[47,56‐59] only [Table 2], with the maximum study being reported on Parkin....

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Journal ArticleDOI
01 Mar 2007-Medicine
TL;DR: Despite increased awareness and recognition and significant inroads into therapeutic frontiers, follow-up remains poor in developing countries and a return to previous level of functioning is not universal.
Abstract: The clinical manifestations of Wilson disease (WD) are varied and challenging. We conducted the current study to present the phenotypic characteristics and follow-up for a large cohort of patients with WD. We reviewed the medical records of 282 cases of WD (male:female ratio, 196:86) for clinical features, investigations, treatment, and outcome data. The clinical presentations were as follows: hepatic, 42 (14.9%); hepato-neurologic, 10 (3.5%); neurologic, 195 (69.1%); pure psychiatric, 7 (2.4%); osseomuscular, 6 (2.1%); and "presymptomatic," 15 (5.3%). Mean age was 15.9 years. Presymptomatic patients and those with the hepatic form of WD were younger and patients with osseomuscular and psychiatric forms were older than neurologic patients. The mean duration of illness at the time of diagnosis was 28 months. Predominant neurologic features were as follows: parkinsonism, 62.3%; dystonia, 35.4%; cerebellar, 28%; pyramidal signs, 16%; chorea, 9%; athetosis, 2.2%; myoclonus, 3.4%; and behavioral abnormalities, 16%. Kayser-Fleischer (KF) rings were seen as follows: neurologic patients, 100%; hepatic patients, 86%; and presymptomatic patients, 59%. Positive family history was noted in 47% and consanguinity in 54%. Patients born of consanguineous parents had an earlier age of onset and shorter duration of illness before presentation. Serum ceruloplasmin was decreased in 93% and 24-hour urinary copper excretion was increased in 70% of patients. Neuroimaging (computed tomography/magnetic resonance imaging) and electrophysiologic abnormalities were seen in many patients. Overall, 195 patients were on D-penicillamine therapy and 182 on zinc sulphate. Follow-up data, available for 225 patients, for a mean duration of 46 months, revealed improvement in 176, no change in 20, and deterioration in 6. Twenty-three patients died. To conclude, despite increased awareness and recognition and significant inroads into therapeutic frontiers, follow-up remains poor in developing countries and a return to previous level of functioning is not universal.

190 citations

Journal ArticleDOI
TL;DR: A door-to-door survey was carried out to screen a community of 14010 people (Parsis living in colonies in Bombay, India) for possible neurologic diseases and found that age-specific prevalence ratios increased consistently with age and age-adjusted prevalence ratios were slightly higher for men.
Abstract: • A door-to-door survey was carried out to screen a community of 14010 people (Parsis living in colonies in Bombay, India) for possible neurologic diseases. High school graduates, social workers, and medical students administered a screening questionnaire that had been shown in a pilot survey to have a sensitivity of 100% for identifying those with Parkinson's disease. Neurologists used defined diagnostic criteria to evaluate individuals positive on the screening survey. There were 46 people (25 men, 21 women) who suffered from Parkinson's disease (328.3 cases per 1000 population). The age-specific prevalence ratios increased consistently with age. Ageadjusted prevalence ratios were slightly higher for men.

126 citations


"Movement disorders: Indian scenario..." refers background or result in this paper

  • ...Higher prevalence of PD among Parsi population is due to higher aged population when compared to national population [Table 1].[12] However the prevalence of PD is lower than many Caucasian populations....

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  • ...Region Author Year of study Population surveyed (R/U) Crude prevalence rate Age adjusted rate West India([12]) Bharucha et al....

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