Kamal Kishore Pandita

Incidence of dementia in a Kashmiri migrant population

Background: Mishriwala is one of five exclusive clusters of Kashmiri migrants established in 1990 to accommodate Kashmiri Pandit families who left Kashmir valley in the wake of militancy. Mishriwala migrant camp has seen minimal immigration and out-migration since its establishment. In an earlier study we reported on the prevalence of dementia amongst a Kashmiri migrant population. That study was conducted in the migrant camp at Mishriwala, 12 km west of Jammu city, the winter capital of Jammu and Kashmir State. We have developed standardized study methods and instruments for use in the Kashmiri-speaking population, which we used for screening for dementia during the prevalence study. We now report the results of a 1-year prospective study carried out to find out the incidence of dementia in the same population. Aim: To ascertain the incidence of dementiain the Kashmiri Pandit population aged 60 years and above. Materials and Methods: A 1-year, prospective, epidemiological study of 186 subjects aged 60 years and above, using cognitive and functional ability screening and clinical evaluation. Results: The incidence of dementia in this population was 5.34 cases per 1000 person-years.

Prevalence of dementia among Kashmiri migrants

Background: Neurological diseases are common disorders resulting in the loss of productive life and disability. Dementia is becoming a major public health problem in the developing world also. Aim: To ascertain the prevalence of dementia among Kashmiri Pandit population aged 60 years and above. Materials and Methods: A cross-sectional survey was conducted among the elderly population of the Kashmiris living in a migrant camp. We developed and used a Kashmiri version of the Mini-Mental State Examination as the test instrument, and a score below 24 was considered indicative of dementia. A functional ability questionnaire was also administered to the subjects. A neurologist carried out the examinations. Results: A sample comprising 200 subjects (95 males and 105 females) were evaluated. The prevalence of dementia is 6.5% among the Kashmiri Pandit population aged 60 years and above, which is higher than that reported from other parts of India.

Active Epilepsy as Indicator of Neurocysticercosis in Rural Northwest India

Objective. To determine the contribution of neurocysticercosis as a cause for active epilepsy and to establish Neurocysticercosis as major definable risk of epilepsy in our setup. Methods. We conducted a door-to-door survey of 2,209 individuals of Bhore Pind and Bhore Kullian villages in Chattah zone of district Jammu (Jumma and Kashmir, Northwest India) to identify patients with symptomatic epilepsy. Patients with active epilepsy were investigated with neuroimaging techniques to establish diagnosis of NCC (neurocysticercosis). Results. Among 25 patients with epilepsy 10(40%) had CT/MR evidence of past or recent NCC infection. This gave us the point prevalence of 4.5/1000 for Neurocysticercosis in our study population. Interpretation. The study shows a high prevalence of NCC accounting for symptomatic epilepsy in our part of India.

Whole Exome Screening Identifies Novel and Recurrent WISP3 Mutations Causing Progressive Pseudorheumatoid Dysplasia in Jammu and Kashmir-India

We report identification and genetic characterization of a rare skeletal disorder that remained unidentified for decades in a village of Jammu and Kashmir, India. The population residing in this region is highly consanguineous and a lack of understanding of the disorder has hindered clinical management and genetic counseling for the many affected individuals in the region. We collected familial information and identified two large extended multiplex pedigrees displaying apparent autosomal recessive inheritance of an uncharacterized skeletal dysplasia. Whole exome sequencing (WES) in members of one pedigree revealed a rare mutation in WISP3:c.156C > A (NP_003871.1:p.Cys52Ter), that perfectly segregated with the disease in the family. To our surprise, Sanger sequencing the WISP3 gene in the second family identified a distinct, novel splice site mutation c.643 + 1G > A, that perfectly segregated with the disease. Combining our next generation sequencing data with careful clinical documentation (familial histories, genetic data, clinical and radiological findings), we have diagnosed the families with Progressive Pseudorheumatoid Dysplasia (PPD). Our results underscore the utility of WES in arriving at definitive diagnoses for rare skeletal dysplasias. This genetic characterization will aid in genetic counseling and management, critically required to curb this rare disorder in the families.

Triggering Risk Factors for Stroke: A Case Crossover Study from a Tertiary Care Hospital in Northwest India

Introduction: The role of traditional risk factors in the pathophysiology of stroke (IS) has been established and is well know. It has recently been shown that 10 risk factors are associated with 90% of the risk of stroke. Material and methods: A case-crossover study design was used for the purpose of study. 2-hour hazard period immediately before the onset of stroke was compared with the 2-hour control period at the same time on the day before the onset of stroke. Results: The study assessed the role of seven potential triggers for stroke. Forty four patients (73%) reported exposure to at least one potential triggering factor during the 2 hours hazard period before onset of stroke symptoms. Twenty nine patients (66%) reported exposure to at least one of three (Anger, sudden change in posture, negative emotions) potential triggers during the 2-hour hazard period. Discussion: The current study examined possible association between exposure to potential triggers during a defined hazard period and triggering of the acute onset of stroke. There have been previously reported observations on the potential effect of emotions as a trigger for MI. Conclusion: The period of study and the study sample may not be large enough for extrapolation but nevertheless does open up a new area for research in our setup.

Inbreeding as a cause for deafness: Dadhkai study

BACKGROUND: We report on the higher prevalence of deaf-mutes from a village in Jammu and Kashmir State of India. MATERIALS AND METHODS: A cross-sectional study among 79 deaf mutes using pedigree analysis, audiometry, imaging and molecular analysis. RESULTS: A high rate of hereditary deafness with 79 individuals diagnosed to be suffering from non-syndrome deafness in a total population of 2452 individuals residing in the village. INTERPRETATION: Flourishing of intermarriages led to a population with high prevalence of deafness

A case report on a novel MT-ATP6 gene variation in atypical mitochondrial Leigh syndrome associated with bilateral basal ganglia calcifications

Leigh Syndrome (LS) is a rare, hereditary progressive neurodegenerative disorder of infancy or early childhood associated with a highly variable clinical presentation even among siblings. Further, genetic heterogeneity makes its diagnosis complicated. Its causative genetic variations are notified in some of the mitochondrial and nuclear genes. Here, we report an atypical case of LS in a 9-year-old boy associated with a novel variation in MT-ATP6 gene. The atypical findings were Bilateral Basal Ganglia Calcification (BGC) and late survival age in the patient. Analyses of the Whole Mitochondrial Genome Sequencing (WMGS) results of the recruited patient and his mother at different read coverage, first at 100× and later repeated at 500×, revealed a novel disease-associated variation in the already known disease-associated MT-ATP6 gene. In conclusion, the present study indicates amalgamation of both neuro-imaging and Next Generation Sequencing (NGS) Technologies aiding the proper diagnosis of LS in atypical cases.

A variation in PANK2 gene is causing Pantothenate kinase-associated Neurodegeneration in a family from Jammu and Kashmir – India

Pantothenate kinase-associated neurodegeneration is a rare hereditary neurodegenerative disorder associated with nucleotide variation(s) in mitochondrial human Pantothenate kinase 2 (hPanK2) protein encoding PANK2 gene, and is characterized by symptoms of extra-pyramidal dysfunction and accumulation of non-heme iron predominantly in the basal ganglia of the brain. In this study, we describe a familial case of PKAN from the State of Jammu and Kashmir (J&K), India based on the clinical findings and genetic screening of two affected siblings born to consanguineous normal parents. The patients present with early-onset, progressive extrapyramidal dysfunction, and brain Magnetic Resonance imaging (MRI) suggestive of symmetrical iron deposition in the globus pallidi. Screening the PANK2 gene in the patients as well as their unaffected family members revealed a functional single nucleotide variation, perfectly segregating in the patient’s family in an autosomal recessive mode of inheritance. We also provide the results of in-silico analyses, predicting the functional consequence of the identified PANK2 variant.

Replication of MACF1 gene variant rs2296172 with type 2 diabetes susceptibility in the Bania population group of Punjab, India

Microtubule actin cross-linking factor 1 (MACF1) gene variant rs2296172 has recently been associated with type 2 diabetes (T2D). However, this variant has never been evaluated as such in Indian populations. In the present replication study, we genotyped variant rs2296172 by Taqman allele discrimination assay in 432 individuals belonging to the Bania caste group from Punjab, India. The single-nucleotide polymorphism (SNP) was evaluated for association with T2D, in a population based candidate gene case-control association study design, by estimating odds ratio with 95% confidence interval. The SNP rs2296172 of MACF1 was found to be significantly associated with T2D (p = 0.02) and odds ratio (OR) = 1.59 (1.06–2.38) at 95% CI . We further emphasize that the Indian population as such is a conglomeration of various endogamous population groups. It is critical that such replication studies be carried out in various populations to find association of variants to T2D susceptibility and understand genetic heterogeneity. However, it is important to avoid pooling of samples to address the concern of population stratification.

Geographic Isolation and Endogamous Practices Provide Higher Risk of Genetic Disorders in Jammu and Kashmir

Rare disorders are poorly understood, most often remain uncharacterized or patients are misdiagnosed due to lack of specific clinical resources. Understanding the basics of inheritance is essential in such cases as it helps to figure out the plausibility of a disorder as an inherited or genetic disease. Though identification and characterization of such disorders is complicated, Next generation Sequencing has come up as a tool in recent times and is of great help. It is quite visible in literature that since the advent of this methodology, a drastic increase in identification and genetic characterization of various rare diseases across the world has occurred. We emphasize on NGS/WES, as an effective method in understanding uncharacterized Mendelian Disorders. It is of great help, especially in developing countries and regions like Jammu and Kashmir where, such familial disorders exist in abundance, due to very high consanguinity, but remain undiagnosed/misdiagnosed due to lack of specialized testing. We have collected huge number of highly extended families representing various rare genetic disorders and trying to elucidate the genetic cause and biology of the diseases in these families. Citation: Rai, E., Angural, A., Sapolia, A., Razdan, S., Pandita, K.K. and Sharma, S. Geographic Isolation and Endogamous Practices Provide Higher Risk of Genetic Disorders in Jammu and Kashmir [Abstract]. In: Abstracts of the NGBT conference; Oct 02-04, 2017; Bhubaneswar, Odisha, India: Can J biotech, Volume 1, Special Issue (Supplement), Page 250. https://doi.org/10.24870/cjb.2017-a234