Rare neurogenetic and neurometabolic disorders comprise a clinically and genetically heterogeneous group of conditions, frequently presenting with overlapping neurological manifestations such as developmental delay, seizures, and cognitive impairment. Whole-exome sequencing (WES) has emerged as a robust approach for elucidating the molecular basis of these disorders. A total of 184 patients with suspected rare neurological disorders were enrolled in this study. Detailed demographic and clinical data were collected, and WES was performed to identify pathogenic and likely pathogenic variants. Variants were annotated and interpreted using standard guidelines, and inheritance patterns were determined. The cohort showed a slight male predominance, with the majority of cases presenting in early childhood (mean age at onset: 29.62 ± 27.69 months). The most common clinical features included developmental delay (82.06
Migraine is a major cause of disability in India, disproportionately affecting women and adolescents. Although traditional pharmacological treatments exist, side effects and poor adherence have increased interest in non-pharmacological options such as remote electrical neuromodulation (REN). However, clinical adoption of REN remains limited because of the absence of clear, India-specific guidelines. An Indian consensus was developed through a two-phase Delphi process involving 49 neurologists. Phase 1 included a scientific committee of eight neurologists who conducted a targeted literature review on REN and formulated 27 consensus statements. In phase 2, 41 neurologists from across India participated in modified Delphi rounds to finalize these statements. Statements achieving over 60
Alzheimer’s disease (AD) shows substantial clinical heterogeneity often caused by genetic variants contributing to both familial and early-onset forms. However, the genetic landscape of AD in the diverse Indian population remains further characterised. To identify probable pathogenic variants associated with AD, representing individuals from Eastern India and to assess their potential structural effects using molecular dynamics (MD) simulations. Whole-exome sequencing was performed in 29 radiologically confirmed AD patients. Variants identified were screened using standard in silico prediction tools and categorised according to their involvement in amyloid precursor protein (APP)-related and non-APP pathways. Molecular dynamics simulations of filtered variants in PSEN1, SORL1, and ABCA7 genes were conducted using GROMACS 2024 to assess conformational stability, flexibility (RMSD, RMSF), compactness (Rg), and solvent accessibility (SASA). Thirty-six variants across 18 genes were identified, including five pathogenic variants and 31 variants of uncertain significance. Frequently affected genes included ABCA7 (8 variants), SORL1 (3 variants), PSEN1 (two novel variants), and APP (London mutation, Val717Ile). Most patients (83.3
Post-stroke cognitive impairment (PSCI) affects nearly 30% of stroke survivors and substantially limits functional recovery. Brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase-beta (Trk beta) signalling plays an important role in synaptic plasticity and cognitive function; however, the contribution of individual NTRK2/Trk beta isoforms to PSCI remains poorly understood. This study investigated (a) isoform-specific NTRK2 mRNA expression, (b) genetic association of the isoform-specific variant rs6559833 with post-stroke cognitive outcomes and (c) DNA methylation patterns potentially regulating NTRK2 expression using blood as primary biosource. Isoform-specific expression was analysed in 50 subjects, rs6559833 was genotyped in 280 ischemic stroke patients, and DNA methylation was assessed in 10 samples using whole-genome bisulfite sequencing. The TRK beta-FL expression was significantly reduced in stroke patients compared with healthy controls, whereas TRK beta-SHC expression was higher in PSCN individuals than in PSCI patients. The latter showed positive correlation with MEK2 expression and memory performance. The 'TT' genotype of the rs6559833 variant showed marginal associations with post-stroke memory status and overall BMSE scores (p = 0.0442 and 0.0488, respectively). Furthermore, hypermethylation was observed within the NTRK2 gene body and in genes encoding its splicing regulators, whereas no evident difference in promoter methylation was observed. Collectively, these findings suggest that Trk beta-SHC expression may be associated with preserved cognitive function after stroke and indicate a potential relationship between isoform-specific NTRK2 expression, genetic regulation and cognitive outcomes in PSCI.
