South Asian medical cohorts reveal strong founder effects and high rates of homozygosity.

The benefits of large-scale genetic studies for healthcare of the populations studied are well documented, but these genetic studies have traditionally ignored people from some parts of the world, such as South Asia. Here we describe whole genome sequence (WGS) data from 4806 individuals recruited from the healthcare delivery systems of Pakistan, India and Bangladesh, combined with WGS from 927 individuals from isolated South Asian populations. We characterize population structure in South Asia and describe a genotyping array (SARGAM) and imputation reference panel that are optimized for South Asian genomes.

Genome-Wide Polygenic Score Predicts Large Number of High Risk Individuals in Monogenic Undiagnosed Young Onset Parkinson's Disease Patients from India.

Parkinson's disease (PD) is a genetically heterogeneous neurodegenerative disease with poorly defined environmental influences. Genomic studies of PD patients have identified disease-relevant monogenic genes, rare variants of significance, and polygenic risk-associated variants. In this study, whole genome sequencing data from 90 young onset Parkinson's disease (YOPD) individuals are analyzed for both monogenic and polygenic risk.

Compound heterozygous variants in Wiskott-Aldrich syndrome like (WASL) gene segregating in a family with early onset Parkinson's disease.

Background: Knowledge of genetic determinants in Parkinson's disease is still limited. Familial forms of the disease continue to provide a rich resource to capture the genetic spectrum in disease pathogenesis, and this approach is exploited in this study.

Methods: Informative members from a three-generation family of Indian ethnicity manifesting a likely autosomal recessive mode of inheritance of Parkinson's disease were used for whole exome sequencing.

Novel and reported variants in Parkinson's disease genes confer high disease burden among Indians.

Background: Genetic heterogeneity in Parkinson's disease (PD) has been unambiguously reported across different populations. Assuming a higher genetic load, we tested variant burden in PD genes to an early onset PD cohort from India.

Methods: Whole exome sequencing was performed in 250 PD patients recruited following MDS-UPDRS criteria.

Early Onset Parkinson's disease due to DJ1 mutations: An Indian study.

Introduction: Early Onset Parkinson's Disease (EOPD) is genetically heterogeneous. PARK2 mutations are the commonest cause of autosomal recessive EOPD followed by PINK1.DJ1 mutations is rare and there is scarce literature on its phenotype and long term outcome.

Evidence of mutations in RIC3 acetylcholine receptor chaperone as a novel cause of autosomal-dominant Parkinson's disease with non-motor phenotypes.

Background: The known genetic determinants of Parkinson's disease (PD) do not explain all cases investigated to date. Contemporary sequencing technologies hold promise for enhanced causal variant discovery. We attempted to identify the putative causal variant in an Indian PD family by whole exome sequencing (WES).

Discovery of a frameshift mutation in podocalyxin-like (PODXL) gene, coding for a neural adhesion molecule, as causal for autosomal-recessive juvenile Parkinsonism.

Background: Mutations in known genes for inherited forms of Parkinson's disease (PD) account for <30% of familial PD (FPD) implying that more causal gene(s) remain to be identified. We attempted to discover the putative causal variant in an Indian family with autosomal-recessive juvenile Parkinsonism (ARJP), tested negative for mutations in PARK2, PINK1 and DJ1.

Methods: Whole exomes of two affected siblings were sequenced.

VPS35 and EIF4G1 mutations are rare in Parkinson's disease among Indians.

Mutations in 2 genes, vacuolar protein sorting homolog 35 (VPS35) and eukaryotic translation initiation factor 4 gamma 1 (EIF4G1), have been recently reported as causal in autosomal dominant Parkinson's disease (PD) among Caucasians. Their contribution to PD in other ethnic groups remains limited with 1% of VPS35 mutations observed in Caucasian and Japanese populations, but none in Chinese, and 11.57% of EIF4G1 mutations in Caucasian families and 0.

Prevalence and profile of Restless Legs Syndrome in Parkinson's disease and other neurodegenerative disorders: a case-control study.

Background: Restless Legs Syndrome (RLS) is associated with impaired central dopaminergic neurotransmission. Though a link between RLS and parkinsonism has been proposed, the prevalence of RLS in parkinsonian disorders is poorly documented.

Objective: To determine the prevalence of RLS in patients with Parkinson's Disease (PD), Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA) and Dementia with Lewy Bodies (DLB).

Leads from xenobiotic metabolism genes for Parkinson's disease among north Indians.

Objective: 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.

Methods: Three hundred and thirty-nine PD patients diagnosed using UK PD brain bank criteria and 344 age-, sex-, and ethnicity-matched controls were recruited.

Role of dysautonomic symptoms in distinguishing Parkinson's disease (PD) from multiple system atrophy (MSA-P) within a year of developing motor symptoms.

Objective: Can dysautonomic symptoms occurring within a year of developing motor symptoms distinguish Multiple system atrophy-Parkinsonian (MSA-P) from Parkinson's disease (PD)?

Patients And Methods: Seventy-two Parkinsonian patients diagnosed as probable PD or MSA-P.

Results: PD (n = 58, 80.6%) and MSA (n = 14, 19.

Evaluation of markers of oxidative stress, antioxidant function and astrocytic proliferation in the striatum and frontal cortex of Parkinson's disease brains.

Dopaminergic neurons die in Parkinson's disease (PD) due to oxidative stress and mitochondrial dysfunction in the substantia nigra (SN). We evaluated if oxidative stress occurs in other brain regions like the caudate nucleus (CD), putamen (Put) and frontal cortex (FC) in human postmortem PD brains (n = 6). While protein oxidation was elevated only in CD (P < 0.

Urogenital symptoms in Parkinson's disease and multiple system atrophy-Parkinsonism: at onset and later.

Methods: One hundred and eighty-one parkinsonian patients were evaluated to determine if urogenital symptoms at presentation to the Neurology clinic can differentiate them as PD or MSA-P. An autonomic questionnaire was used to document urinary and genital symptoms.

Results: Mean age at presentation and disease duration in PD and MSA-P were similar.

Role of polymorphisms in dopamine synthesis and metabolism genes and association of DBH haplotypes with Parkinson's disease among North Indians.

Objectives: Genetic and non-genetic components are believed to govern the etiology of common complex traits such as Parkinson's disease (PD). In view of the biochemical evidence of depleted dopamine levels in the affected brains and also the most common and effective therapeutic modality of administration of levodopa in PD, genes from the dopaminergic pathway emerge as major determinants. We have earlier shown the role of DRD4-120 bp duplication marker in PD susceptibility.

Are current recommendations to diagnose orthostatic hypotension in Parkinson's disease satisfactory?

We interviewed 50 Parkinson's disease (PD) patients using a questionnaire to verify the reliability of orthostatic symptoms in warning the presence of orthostatic hypotension (OH). OH is defined as 20 mm Hg systolic or 10 mm Hg diastolic BP fall within 3 min of tilting or standing but if this fall occurs after 3 min we called it 'late OH' (L-OH). We compared if OH in Parkinson's disease (PD) was more frequent after head-up tilt or on standing and if the period of postural challenge matters in detecting OH.

Biotin-responsive basal ganglia disease: a treatable and reversible neurological disorder of childhood.

Biotin-responsive basal ganglia disease is a rare childhood neurological disorder of uncertain etiology that is treatable if suspected and diagnosed. Only few cases have been reported earlier in literature. We report a case of biotin-responsive basal ganglia disease suspected clinically, corroborated by neuroimaging and a dramatic response to biotin therapy.

Primary cardiac cytotoxic T-cell lymphoma presenting with neurological deficits: a case report.

Background: Primary cardiac lymphoma is extremely rare in immunocompetent patients. Clinical manifestations vary, and, most often, diagnosis is not made until autopsy. The majority of reported primary cardiac lymphoma cases have been of B-cell origin, while T-cell cardiac lymphomas have been extremely rare.

Elemental mercury poisoning probably causes cortical myoclonus.

Mercury toxicity causes postural tremors, commonly referred to as "mercurial tremors," and cerebellar dysfunction. A 23-year woman, 2 years after injecting herself with elemental mercury developed disabling generalized myoclonus and ataxia. Electrophysiological studies confirmed the myoclonus was probably of cortical origin.

Perspectives towards predictive testing in Huntington disease.

Objective: Genetic counseling for individuals undergoing presymptomatic testing is lacking in India although testing is easily available. This has an impact on family members of Huntington's disease (HD), an autosomal dominant disease, wherein the age at onset of symptoms varies.

Aim: We examine if attitudes differ towards presymptomatic testing for HD amongst HD family members, physicians and laypersons.

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.