Genetic and molecular mechanisms of the FOXP2-CNTNAP2 pathway in Autism spectrum disorders and speech disorders

GENETIC AND MOLECULAR MECHANISMS IN PEDIATRIC NEUROLOGICAL DISORDERS: A SYSTEMATIC REVIEW

The study provides an integrated framework linking genetic variation to molecular dysfunction and clinical outcomes, offering valuable insights for future research and therapeutic development in pediatric neurology.

Gene Signalling Pathways, Putative Biomarkers and Hypothetical Modulation in Autism Spectrum Disorders

Abstract. Autism spectrum disorder (ASD) is one of the most common neurological disorders, with a ubiquitous in-crease in prevalence. A theoretical rationale is providing for identifying potentially clinically significant diagnostic bi-omarkers and opportunities for targeted pharmacological modulation based on current data on gene signaling path-ways. This systematic review is based on data from systematic reviews and meta-analyses devoted to the basic aspects of autism spectrum disorder. This has made it possible to outline approaches to syndrome-associated diagnosis and treatment strategies. This article explores integrative pathogenetic mechanisms of ASD, encompassing prenatal viral exposure, alterations in serotonin and oxytocin signaling pathways, regulation of N-methyl-D-aspartate receptors, SHANK proteins, and members of the Solute Carrier protein family. Immune, viral, and metabolic factors, neurotrans-mitter systems, synaptic proteins and structural regulation, biomarkers, and therapeutic strategies were detected as di-agnostic and modulation promising in ASD. The potential of combined modulation involving retinoic acid derivatives, folates, antioxidants, neurotrophins, oxytocin preparations, glycine, and magnesium has been demonstrated, depending on the syndromic manifestation of ASD. A possible role of the rubella virus in prenatal disruption of retinoic acid me-tabolism and subsequent impairment of neuronal pathway formation has been demonstrated, as well as the specific in-fluence of the COVID-19 virus on the IGF-1 signaling pathway. An association has been proposed between autoimmune activation during impaired neuronal maturation and ferroptosis processes, resulting in decreased ferritin and transfer-rin levels in children with ASD. Analysis of the literature explores the potential for more selective diagnosis and modu-lation in ASD using specific biomarkers and to indicate directions for future research.

Unraveling the impact of trip12 on neurodevelopment: insights from a zebrafish model

This study provides substantial evidence for the vital role of trip12 in the early stages of development, as homozygous individuals exhibited early mortality by Day 23 post-fertilization, while a substantial mortality rate was observed by Day 35 in ‘heterozygous’ mutants.

Investigation of WNT2, DISC1, and DOCK4 polymorphisms in a Turkish autism spectrum disorder cohort: a case–control and bioinformatics analysis

CMIP as a novel candidate gene for neurodevelopmental and neuropsychiatric disorders

Multi-omic data integration improves the resolution of the molecular etiology of autism in a mouse model.

Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder with complex molecular etiology. Since genetic causes account for less than 50% of ASD cases, novel approaches are required to overcome the challenges of characterizing genes and molecular pathways linking risk alleles to phenotype. Here we use RNA-sequencing, 3-dimensional protein-centric chromatin conformation (Hi-ChIP), and whole genome DNA methylation sequencing approaches to investigate hippocampal tissue from an ASD mouse model (Cntnap2 knockout [Cntnap2 KO]) to determine if multi-omic data integration improves the resolution of key molecular pathways contributing to the complex ASD phenotype. Each -omic dataset individually identified disruptions in numerous genes and pathways, providing broad ASD-related insights, such as 1) 699 downregulated genes with an enrichment of neuronal ontological terms; 2) unique chromatin interactions in Cntnap2 KO mice; and 3) that most differentially methylated genes (1220/1659) have a neuronal function. The multi-omic data integration reduced the heterogeneity and refined the data to 43 genes with links to ASD (e.g., Zbtb18, Cttnbp2, Gabbr2). A pathways analysis of these 43 genes identified one gene ontological term: regulation of neuronal synaptic plasticity. These findings are consistent with large scale gene expression studies of human ASD postmortem brain tissue, suggesting that multi-omic data integration can be used to achieve a greater resolution of the heterogeneous ASD molecular etiology.