Search

Your search keyword '"Thelma, B. K."' showing total 365 results
Start Over Author "Thelma, B. K."
365 results on '"Thelma, B. K."'

10. Effort to differentiate essential tremor plus and dystonic tremor using whole exome sequencing: an exploratory study.

Author

Pandey, Sanjay, Yadav, Navneesh, Dinesh, Shreya, Rawat, Chandra Shekhar, and Thelma, B. K.

Subjects
TREMOR, EXOMES, DNA sequencing, GENOTYPES, PHENOTYPES
Abstract

Background: The clinical differentiation between essential tremor plus (ETP) and dystonic tremor (DT) is challenging. This study aimed at the genetic diagnosis of ETP and DT. Methods: Whole exome sequencing was performed on 50 probands (ETP = 25; DT = 25) and analysed to identify variants in known genes linked with dystonia and essential tremor plus phenotypes. Results: We identified pathogenic/likely pathogenic variants [THAP1 (n = 1) and ANO3 (n = 1)] in two patients with DT. In addition, one DT patient had a variant of uncertain significance in FUS and four patients had benign variants [CIZ1 (n = 1), COL6A3 (n = 1), GCH1 (n = 1), TENM4 (n = 1)]. One patient with ETP was detected to have a variant of uncertain significance in TENM4 and five patients with ETP had benign variants [COL6A3 (n = 2), VPS16 (n = 1), TAF1 (n = 1), KMT2B (n = 1)]. Conclusion: Genetic studies may be in an important biomarker in differentiating patients with ET plus from DT which is challenging in a clinical setting. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

15. FMR1 gene CGG repeat distribution among the three individual cohorts with intellectual disability, autism, and primary ovarian insufficiency from Tamil Nadu, Southern India

Author

Indhumathi Nagarathinam, Samuel S. Chong, Thelma B. K., Jeffrey Justin Margret, Viswanathan Venkataraman, Karthikeyen Natarajan Padmavathy, and C. R. Srikumari Srisailapathy

Subjects
autism spectrum disorder, CGG repeat variation, fragile X syndrome, intellectual disability, primary ovarian insufficiency, Genetics, QH426-470
Abstract

Abstract Fragile X syndrome is the most common genetic cause of intellectual disability (ID) and is also well known to have a role in primary ovarian insufficiency (POI) and fragile X‐associated tremor ataxia syndrome (FXTAS) that expresses across generations. The objective was to compare the CGG repeat variants in FMR1 gene among three correlating cohorts of ID, autism and idiopathic POI. Thirty‐six patients with ID, 12 with autism spectrum disorder (ASD) and 13 females with idiopathic POI were screened for FMR1 CGG repeat size by fluorescent methylation‐specific PCR and GeneScan analysis, irrespective of Hagerman checklist clinical scores. Among 29 males and seven females, 11 FMR1 allelic variants ranging from 21 to >200 CGG repeats were observed. Three (CF2‐3, 39‐5, 44‐2) out of 29 males had full mutation alleles accounting for a 10.34% incidence of FXS among idiopathic ID males. One of them was a mosaic for CGG repeats with both premutation and full mutation alleles. The frequency of fragile X syndrome is high among patients with idiopathic ID; they also had a high score for the clinical check list. A cascade testing that begins with checklist evaluation prior to DNA analysis will be cost‐effective for establishing early diagnosis in South India. With the huge disease burden, there is a need for the establishment of more molecular diagnostics and self‐help groups for fragile X syndrome.

Published
2021
Full Text
View/download PDF

27. Building polarization into protein-inhibitor binding dynamics in rational drug design for rheumatoid arthritis

Author

Sandhu, Gurvisha, Agrawal, Praveen, Bose, Surojit, and Thelma, B. K.

Abstract

Standard force field-based simulations to accomplish structure-based evaluations of lead molecules is a powerful tool. Combining protein fragmentation into tractable sub-systems with continuum solvation method is envisaged to enable quantum mechanics-based electronic structure calculations of macromolecules in their realistic environment. This along with incorporation of many-body polarization effect in molecular dynamics simulations may augment an accurate description of electrostatics of protein-inhibitor systems for effective drug design. Rheumatoid arthritis (RA) is a complex autoimmune disorder plagued by the ceiling effect of current targeted therapies, encouraging identification of new druggable targets and corresponding drug design to tackle the refractory form of disease. In this study, polarization-inclusive force field approach has been used to model protein solvation and ligand binding for ‘Mitogen-activated protein kinase’ (MAP3K8), a regulatory node of notable pharmacological relevance in RA synovial biology. For MAP3K8 inhibitors belonging to different scaffold series, the calculations illustrated differential electrostatic contribution to their relative binding affinities and successfully explained examples from available structure-activity relationship studies. Results from this study exemplified i) the advantage of this approach in reliably ranking inhibitors having close nanomolar range activities for the same target; and ii) its prospective application in lead molecule identification aiding drug discovery efforts in RA. Communicated by Ramaswamy H. Sarma

Published
2023
Full Text
View/download PDF

33. Stratification of rheumatoid arthritis cohort using Ayurveda based deep phenotyping approach identifies novel genes in a GWAS

Author

Juyal, Garima, Pandey, Anuj, Garcia, Sara L., Negi, Sapna, Gupta, Ramneek, Kumar, Uma, Bhat, Bheema, Juyal, Ramesh C., Thelma, B. K., Juyal, Garima, Pandey, Anuj, Garcia, Sara L., Negi, Sapna, Gupta, Ramneek, Kumar, Uma, Bhat, Bheema, Juyal, Ramesh C., and Thelma, B. K.

Abstract

Background and aim: Genome wide association studies have scaled up both in terms of sample size and range of complex disorders investigated, but these have explained relatively little phenotypic variance. Of the several reasons, phenotypic heterogeneity seems to be a likely contributor for missing out genetic associations of large effects. Ayurveda, the traditional Indian system of medicine is one such tool which adopts a holistic deep phenotyping approach and classifies individuals based on their body constitution/prakriti. We hypothesized that Ayurveda based phenotypic stratification of healthy and diseased individuals will allow us to achieve much desired homogeneous cohorts which would facilitate detection of genetic association of large effects. In this proof of concept study, we performed a genome wide association testing of clinically diagnosed rheumatoid arthritis patients and healthy controls, who were re-phenotyped into Vata, Pitta and Kapha predominant prakriti sub-groups. Experimental procedure: Genotypes of rheumatoid arthritis cases (Vata = 49; Pitta = 117; Kapha = 78) and controls (Vata = 33; Pitta = 175; Kapha = 85) were retrieved from the total genotype data, used in a recent genome-wide association study performed in our laboratory. A total of 528461 SNPs were included after quality control. Prakriti-wise genome-wide association analysis was employed. Results and conclusion: This study identified (i) prakriti-specific novel disease risk genes of high effect sizes; (ii) putative candidates of novel therapeutic potential; and (iii) a good correlation between genetic findings and clinical knowledge in Ayurveda. Adopting Ayurveda based deep phenotyping may facilitate explaining hitherto undiscovered heritability in complex traits and may propel much needed progress in personalized medicine.

Published
2022

39. Prediction of Inflammatory Bowel Diseases using Genetic Risk Score in Asian populations

Author

Siew C. Ng, Michiaki Kubo, Atsushi Takahashi, Behrooz Z. Alizadeh, Jae Hee Cheon, Thelma B K, Keiko Yamazaki, Ajit Sood, Homayoon Vahedi, Suzanne van Sommeren, Reza Malekzadeh, Suk-Kyun Yang, Nasser Ebrahimi Daryani, Rinse K. Weersma, Sunny H. Wong, Rupa Banerjee, Won Ho Kim, and Shifteh Abedian

Subjects
medicine.medical_specialty, business.industry, Internal medicine, fungi, medicine, Inflammatory Bowel Diseases, Genetic risk, business, digestive system diseases
Abstract

Background and Aims: The incidence of Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and Ulcerative colitis (UC), is rising in Asian populations. We undertook a cross-population study to explore whether genetic risk scores (GRS) of IBD, CD and UC could explain their occurrence, and whether they can be used to predict disease occurrence in general populations from East Asia (EA) and Central Asia (CA). Methods We studied 9,698 subjects – 4,733 IBD patients (2,003 CD; 2,730 UC) and 4,965 matched controls – who had been genotyped using Immunochip. The subjects were from three East Asian (Japan, South Korea and China) and two Central Asian populations (India and Iran). We generated GRS for each population by combining information from up to 201 genome-wide significant IBD-associated variants to summarize the total load of genetic risk for each phenotype. We then estimated the explained variance and predictability of IBD using the GRS. Results IBD GRS could explain up to 4.40% and 4.14% of IBD variance at a significant level in East Asian and Central Asian populations, respectively, but, given a prevalence of 0.01% and 0.04% for IBD, these yield limited predictive probability. GRS for CD and UC separately proved less significant than GRS for IBD. Conclusion GRS alone can explain only a limited percentage of disease occurrence (

Published
2021

41. Pre-prescription testing in psychiatry: an overview.

Author

Mukhopadhyay, Anirban, Rai, Chandra Bhushan, Deshpande, Smita N, and Thelma, B. K.

Subjects
PHARMACOGENOMICS, NEUROBEHAVIORAL disorders, ANTIPSYCHOTIC agents
Abstract

Drug therapy ‘tailored’ towards an individual based on his/her genetic profile is becoming increasingly popular in the era of personalised medicine. Pre-prescription testing which enables this, exploits the link between a relevant set of genetic variants and drug metabolism profile to maximise drug efficacy and lower the risk of adverse drug reactions. Since the conception over 50 years ago that drug response might be linked to underlying genetic makeup, the science around this field has evolved rapidly across a wide range of drugs including antipsychotics. Over 80% of both typical and atypical antipsychotics are known to be metabolised by phase-I drug metabolising enzymes such as cytochrome P450 (CYP450) family of genes which harbour extensive genetic variations. This has encouraged variant testing in these genes among patients with neuropsychiatric disorders. A confluence of accelerated variant discovery and next generation sequencing offers a fast and cost-effective approach. However, genomic literacy among the end users, i.e., the psychiatrists, patients, and their primary caregivers remains low, posing a major hindrance in the realisation of this pharmacogenetic goal. A well-oiled, multi-disciplinary machinery comprising of researchers, psychiatrists, and genetic counsellors would be the key for optimal dissemination of this intervention. This review presents a broad conceptual background of pharmacogenetics/pharmacogenomics, its potential in psychiatry in particular, together with clinical evidence, and the accompanying challenges for its effective implementation in clinical settings. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results