Proinflammatory phenotype can be critical in defining and modulating the genetic risk of non-syndromic hearing loss.

Non-syndromic hearing loss (NSHL) is a common sensory disorder with a multifactorial origin, involving both genetic and environmental components. Its genetic basis shows significant variability and incomplete penetrance across populations. Environmental factors, especially TORCH infections and sterile inflammation, may contribute to NSHL by triggering inflammatory cascades.

Integrated Pharmacoepigenomic Analysis Uncovers the Impact of Antiseizure Medications on Developmental Pathways and the Protective Effect of Folic Acid.

Fetal exposure to antiseizure medications (ASMs) can impact organogenesis, resulting in elevated risk of congenital malformations. Despite longstanding clinical awareness of the teratogenic potential of ASMs, the molecular mechanisms remain largely unexplored. To address this multisystem impact of ASMs, an OMIC-based approach was considered to understand the impact of ASMs on methylome and subsequently on proteome and how folic acid (FA) supplementation can counter the teratogenic impact.

Cross-Talk Between Hypoxia-Inducible Factors in Driving the Pathology of Oral Squamous Cell Carcinoma: An Immunohistochemical Analysis of the Role of Hypoxia-Inducible Factors and Cancer-Associated Fibroblasts.

Background: Tumor hypoxia refers to reduced oxygen levels in tumor tissues, and the transcription factors of cellular response to hypoxia are hypoxia-inducible factors (HIFs). Although the altered expression of HIFs has been identified in many malignancies, their role in oral squamous cell carcinoma (OSCC) is still debatable. Cancer-associated fibroblasts (CAF) are part of the tumor microenvironment; however, the effects of hypoxia on CAFs require further investigation.

Pro-inflammatory cytokine genetic variants show variable susceptibility to mild cognitive impairment, alzheimer's disease and frontotemporal dementia in South India.

Dementia is a general term for loss of memory, ling and other thinking abilities that are severe enough to interfere with daily life. It is very crucial to distinguish the different forms of dementia such as Alzheimer's disease (AD), frontotemporal dementia (FTD) and amnestic mild cognitive impairment (MCI) at phenotypic and genetic level. In India, the estimated prevalence of dementia for adults more than 60 years old is reported to be 7.

Whole Exome Sequencing Study of a Multizygotic Quadruplet Discordant for Autism Spectrum Disorder Reveals Novel Autism Candidate Genes.

Autism spectrum disorder (ASD) is a childhood-onset complex neurodevelopmental disorder. We carried out a comprehensive genetic study of a quadruplet discordant for ASD to identify the candidate genes of ASD. Whole exome sequencing (WES) was done for the quadruplet and their parents.

Neur-Ally: a deep learning model for regulatory variant prediction based on genomic and epigenomic features in brain and its validation in certain neurological disorders.

Large-scale quantitative studies have identified significant genetic associations for various neurological disorders. Expression quantitative trait locus (eQTL) studies have shown the effect of single-nucleotide polymorphisms (SNPs) on the differential expression of genes in brain tissues. However, a large majority of the associations are contributed by SNPs in the noncoding regions that can have significant regulatory function but are often ignored.

A real-world comparison between the diagnostic yield of trio-whole exome sequencing and proband-only targeted exome sequencing in complex childhood epilepsy.

Purpose: Exome sequencing is the preferred method for the molecular diagnosis of childhood drug-resistant epilepsies (DRE) of uncertain etiology, particularly the developmental and epileptic encephalopathies (DEE) with a challenge being genotype-phenotype heterogeneity. This study assesses the diagnostic utility of trio-whole exome sequencing (trio-WES) over a panel-based targeted exome sequencing (TES).

Methods: We performed genetic testing in 400 probands (age of onset <12 years) who had been diagnosed with complex pediatric epilepsy syndromes (refractory focal/generalized epilepsies of uncertain etiology and DEE).

Rare Pathogenic Variants Identified in Whole Exome Sequencing of Monozygotic Twins With Autism Spectrum Disorder.

Background: Autism spectrum disorder (ASD) is a childhood-onset complex neurodevelopmental disorder characterized by problems with communication and social interaction and restricted, repetitive, stereotyped behavior. The prevalence of ASD is one in 36 children. The genetic architecture of ASD is complex in spite of its high heritability.

Comprehensive Genetic Study of a Monozygotic Triplet Discordant for Autism Spectrum Disorder.

There are a few comprehensive genetic studies on autism spectrum disorders (ASD) in India. Children of multiple births are valuable for genomics studies of complex disorders such as ASD. We report whole-exome sequencing (WES) in a triplet family in which only one among the triplet has ASD.

Methylome-wide and meQTL analysis helps to distinguish treatment response from non-response and pathogenesis markers in schizophrenia.

Schizophrenia is a complex condition with entwined genetic and epigenetic risk factors, posing a challenge to disentangle the intermixed pathological and therapeutic epigenetic signatures. To resolve this, we performed 850K methylome-wide and 700K genome-wide studies on the same set of schizophrenia patients by stratifying them into responders, non-responders, and drug-naïve patients. The key genes that signified the response were followed up using real-time gene expression studies to understand the effect of antipsychotics at the gene transcription level.

Genetic variant interpretation for the neurologist - A pragmatic approach in the next-generation sequencing era in childhood epilepsy.

Genetic advances over the past decade have enhanced our understanding of the genetic landscape of childhood epilepsy. However a major challenge for clinicians ha been understanding the rationale and systematic approach towards interpretation of the clinical significance of variant(s) detected in their patients. As the clinical paradigm evolves from gene panels to whole exome or whole genome testing including rapid genome sequencing, the number of patients tested and variants identified per patient will only increase.

Impact of variant subtype on electro-clinical phenotype of Dravet syndrome- a South Indian cohort study.

Objective: We aimed to compare the electroclinical correlates of truncating and missense variants of SCN1A variants in children with Dravet syndrome (DS) and to determine phenotypic features in relation to variants identified and seizure outcomes.

Methods: A single center prospective study was carried out on a South Indian cohort. Patients below 18 years of age who met the clinical criteria for DS who had undergone genetic testing and completed a minimum of one year follow up were included.

Metabolic causes of pediatric developmental & epileptic encephalopathies (DEE)- genetic variant analysis in a south Indian cohort.

Purpose: Drug-resistant epilepsy is seen in patients with inborn errors of metabolism and metabolic dysfunction in neurons is crucial to brain disorders associated with psychomotor impairment. Diagnostic rates of metabolic causes of developmental and epileptic encephalopathy (DEE) using next generation sequencing have been rarely studied in literature.

Methods: A prospective hospital study was carried out in 384 children with DEE, who underwent genetic testing.

An interpretable block-attention network for identifying regulatory feature interactions.

The importance of regulatory features in health and disease is increasing, making it crucial to identify the hallmarks of these features. Self-attention networks (SAN) have given rise to numerous models for the prediction of complex phenomena. But the potential of SANs in biological models was limited because of high memory requirement proportional to input token length and lack of interpretability of self-attention scores.

Effects of a six-month yoga intervention on the immune-inflammatory pathway in antipsychotic-stabilized schizophrenia patients: A randomized controlled trial.

Background: Schizophrenia is a complex neuropsychiatric disorder for which several etiopathological theories have been proposed, one of the prominent ones being immune dysfunction. Recent studies on yoga as an add-on therapy have shown improvement in negative symptoms, cognition, and quality of life in schizophrenia patients. However, the biological mechanism/s of action of yoga in schizophrenia are not clear.

Arginase deficiency-An unheralded cause of developmental epileptic encephalopathy.

Arginase deficiency, which leads to hyperargininaemia is a rare urea cycle disorder caused by a mutation in the ARG1 gene. It is an under-recognized cause of pediatric developmental epileptic encephalopathy, with the key coexistent clinical features being developmental delay or regression and spasticity. Detection of ARG1 gene mutation on genetic testing is the confirmatory diagnostic test.

Contribution from MHC-Mediated Risk in Schizophrenia Can Reflect a More Ethnic-Specific Genetic and Comorbid Background.

The immune system seems to play a significant role in the development of schizophrenia. This becomes more evident with the emerging role of MHC complex and cytokines in schizophrenia. In the recent past, several GWAS have implied that the 6p21 region was associated with schizophrenia.

Understanding Pharmaco-Epigenomic Response of Antipsychotic Drugs Using Genome-Wide MicroRNA Expression Profile in Liver Cell Line.

Interindividual variability in drug response is a major concern among patients undergoing antipsychotic drug treatment. Apart from genetic and physiological factors, this variability in drug response could also be attributed to epigenetic mechanisms. The microRNAs (miRNAs) are key epigenetic markers that play an important role in pathogenesis and drug response.

Association between matrix metalloproteinases-2 and -9 gene polymorphism with basement membrane disruption in oral lichen planus: A case-control pilot study.

Objectives: This study investigated genetic polymorphism of matrix metalloproteinases (MMP) -2 and -9 in oral lichen planus (OLP) and their association with the basement membrane status.

Study Design: This case-control study involved genotyping of peripheral blood sample of 32 OLP patients and 106 ethnically matched controls. Single nucleotide polymorphisms (SNP) that were assessed in the groups were- rs3918242, rs17576 and rs865094.