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
Background: Poststroke cognitive impairment (PSCI) affects nearly 30% of stroke survivors and significantly impairs functional recovery. Brain derived neurotrophic factor (BDNF)tropomyosin receptor kinase beta; (Trk beta) signalling is crucial for synaptic plasticity and cognitive function. While altered expression of truncated TRK beta T1 isoforms has been linked to stroke, the contribution of the TRK beta SHC isoform to PSCI in humans remains poorly understood. Objectives: This study aimed to (i) assess isoform-specific expression changes of NTRK2 associated with PSCI, (ii) evaluate the role of an isoform specific genetic variant in disease susceptibility, and (iii) identify DNA methylation changes regulating NTRK2 expression (if any). Methods: Gene expression levels of three major NTRK2 isoforms and MEK2 were analyzed in peripheral blood mononuclear cells from 19 PSCI patients, 21 post stroke cognitively normal (PSCN) individuals, and 11 healthy controls. Expression data were correlated with raw memory scores and MEK2 expression. DNA methylation profiles of NTRK2 and its transcriptional regulators were assessed using whole-genome bisulfite sequencing. Results: TRK beta FL expression was significantly reduced in stroke patients compared with controls. In contrast, TRKbeta SHC expression was elevated in PSCN individuals relative to PSCI cases and showed a positive correlation with MEK2 expression and memory performance. No significant association was observed between rs65339833 and cognitive subdomains. Gene body hypermethylation, but not promoter methylation, was detected in NTRK2 and its regulatory genes. Conclusions: Elevated TRK& beta SHC expression may contribute to preserved cognitive function following stroke. DNA methylation status of NTRK2 may regulate alternative splicing and thus represent a novel therapeutic avenue for preventing or mitigating PSCI. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study has been supported by Post-Doctoral fellowship grants from the Department of Science & Technology, Govt. of India, under WISE-PDF Programme to first and Corresponding author DS [DST/WISE-PDF/LS-1/2024], Department of Science & Technology and Biotechnology, Govt. of West Bengal to AB [STBT-11012(19)/15/2024-ST SEC]. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Ethics Committee, Nil Ratan Sircar Medical College, Kolkata, approved the study protocol (Memo No: NRSMC/IEC/89/2021, Date: 23.12.2021 and NRSMC/IEC/038/2025, Date: 07.03.2025). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The datasets generated and/or analyzed during the current study are not publicly available due to ongoing parallel studies involving novel observations, as well as planned future publications arising from downstream analyses of these datasets. However, the data are available from the corresponding author upon reasonable request.
