Journal of neurogenetics最新文献

This study investigates the genetic causes of epilepsy in 166 paediatric patients under the age of 16 from the East Anatolian region of Turkey, who were treated at Erzurum City Hospital between 2018 and 2023. Patients with early-onset seizures, a family history of epilepsy or intellectual disability was selected for genetic analysis using a next-generation sequencing (NGS) gene panel targeting 449 genes associated with epilepsy and epileptic encephalopathy. The analysis revealed that pathogenic or probable pathogenic mutations were present in 14.8% (32 patients), highlighting the significant role of genetic factors in the aetiology of epilepsy in this population. In addition, 30.6% (66 patients) carried variants of uncertain significance (VUS), which, although not classified as pathogenic, have potential clinical relevance. Many epilepsy-related genes follow an autosomal dominant inheritance pattern, meaning that VUSs may gain pathogenic significance as more data and global studies accumulate, emphasising the evolving nature of genetic research. In addition to genetic factors, other aetiological causes such as perinatal insults (15.3%) and infections (7.9%) were identified, highlighting the multifactorial origin of epilepsy. While pathogenic mutations currently serve as important diagnostic and therapeutic markers, the role of VUS should not be underestimated. Genetic testing has proven to be essential for understanding the complex causes of epilepsy, providing opportunities for personalised treatment and genetic counselling. This study highlights the importance of genetic testing in regions such as Eastern Anatolia, where both environmental and genetic factors may influence the prevalence of epilepsy. As genetic databases expand, it is likely that the understanding of VUS will evolve, improving the clinical management of epilepsy through more targeted therapies and improved outcomes.

The study of olfaction in Drosophila melanogaster has greatly benefited from genetic reagents such as olfactory receptor mutant lines and GAL4 reporter lines. The CRISPR/Cas9 gene-editing system has been increasingly used to create null receptor mutants or replace coding regions with GAL4 reporters. To further expand this toolkit for manipulating fly olfactory receptor neurons (ORNs), we generated null alleles for 11 different olfactory receptors by using CRISPR/Cas9 to knock in LexA drivers, including multiple lines for receptors which have thus far lacked knock-in mutants. The targeted neuronal types represent a broad range of antennal ORNs from all four morphological sensillum classes. Additionally, we confirmed their loss-of-function phenotypes, assessed receptor haploinsufficiency, and evaluated the specificity of the LexA knock-in drivers. These receptor mutant lines have been deposited at the Bloomington Drosophila Stock Center for use by the broader scientific community.

Molecular studies identifying alterations associated with PTSD have predominantly focused on candidate genes or conducted genome-wide analyses, often encountering issues with replicability. This review aims to identify robust bi-directional epigenetic and microRNA (miRNA) regulators focusing on their functional impacts on post-traumatic stress disorder (PTSD) and their utility in clinical diagnosis, whilst examining knowledge gaps in the existing research. A systematic search was conducted across multiple databases, including Web of Science, Scopus, Global Health (CABI), and PubMed, augmented by grey literature, yielding 3465 potential articles. Ultimately, 92 studies met the inclusion criteria and were analysed to pinpoint significant epigenetic changes with clinically relevant potential in PTSD. The selected studies explored histone modifications, CpG sites, single nucleotide polymorphisms (SNPs), and miRNA biomarkers. Specifically, nine studies examined epigenetic markers, detailing the influence of methylation on chromatin accessibility at histone positions H3K4, H3K9, and H3K36 within a PTSD context. Seventy-three studies investigated DNA methylation, identifying 20 hypermethylated and five hypomethylated CpG islands consistently observed in PTSD participants. Nineteen studies linked 88 SNPs to PTSD, with only one SNP replicated within these studies. Furthermore, sixteen studies focused on miRNAs, with findings indicating 194 downregulated and 24 upregulated miRNAs were associated with PTSD. Although there are epigenetic mechanisms that are significantly affected by PTSD, a granular deconstruction of these mechanisms elucidates the need to incorporate more nuanced approaches to identifying the factors that contribute to PTSD. Technological advances in diagnostic tools are driving the need to integrate detailed participant characteristics, trauma type, genetic susceptibilities, and best practices for robust reporting. This comprehensive approach will be crucial for enhancing the translational potential of PTSD research for clinical application.

SMA (spinal muscular atrophy) is an autosomal recessive neuromuscular disease that causes muscle atrophy and weakness. SMA is diagnosed by a homozygous deletion in exon 7 of the SMN1 gene. However, mutations in genes located in the SMA region, such as SMN2, NAIP, SERF1, and GTF2H2, may also contribute to the severity of the disease. Within our study's scope, 58 SMA patients who applied in 2018-2021 and 40 healthy controls were analyzed. The study retrospectively included the SMN1 and SMN2 copy numbers previously determined by the MLPA method. Then, NAIP gene analyses with the multiplex PCR method and GTF2H2 gene analyses with the RFLP method were performed. There was a significant correlation (p = 0.00001) between SMN2 copy numbers and SMA subtypes. Also, the NAIP gene (p = 0.01) and the GTF2H2 gene (p = 0.0049) revealed a significant difference between healthy and SMA subjects, whereas the SMA subtypes indicated no significant differences. We detected a significant correlation between clinical subtypes and HFMSE scores in 32 pediatric SMA patients compared (p = 0.01). While pediatric patients with GTF2H2 deletions demonstrated higher motor functions, and those with NAIP deletions demonstrated lower motor functions. In this study, we examined the relationship between NAIP and GTF2H2, called SMN region modifier genes, and the clinical severity of the disease in Turkish SMA patients. Despite its small scale, this research will benefit future investigations into the pathogenesis of SMA disease.

Egg-laying is one of the key aspects of female reproductive behavior in insects. Egg-laying has been studied since the dawn of Drosophila melanogaster as a model organism. The female's internal state, hormones, and external factors, such as nutrition, light, and social environment, affect egg-laying output. However, only recently, neurobiological features of egg-laying behavior have been studied in detail. fruitless and doublesex, two key players in the sex determination pathway, have become focal points in identifying neurons of reproductive significance in both central and peripheral nervous systems. The reproductive tract and external terminalia house sensory neurons that carry the sensory information of egg maturation, mating and egg-laying. These sensory signals include the presence of male accessory gland products and mechanical stimuli. The abdominal neuromere houses neurons that receive information from the reproductive tract, including sex peptide abdominal ganglion neurons (SAGs), and send their information to the brain. In the brain, neuronal groups like aDNs and pC1 clusters modulate egg-laying decision-making, and other neurons like oviINs and oviDNs are necessary for egg-laying itself. Lastly, motor neurons involved in egg-laying, which are mostly octopaminergic, reside in the abdominal neuromere and orchestrate the muscle movements required for laying the egg. Egg-laying neuronal control is important in various evolutionary processes like cryptic female choice, and using different Drosophila species can provide intriguing avenues for the future of the field.

Glioblastoma multiforme (GBM) is an aggressive and diffuse type of glioma with the lowest survival rate in patients. The recent failure of multiple treatments suggests that targeting several targets at once may be a different strategy to overcome GBM carcinogenesis. Normal function of oncogenes and tumor suppressor genes need for the preservation of regular cellular processes, so any defects in these genes' activity, operate the corresponding signaling pathways, which initiate carcinogenic processes. Long non-coding RNAs (lncRNAs) that can be found in the cytoplasm or nucleus of the cells, control the transcription and translation of genes. LncRNAs perform a variety of functions, including epigenetic alteration, protein modification and stability, transcriptional regulation, and competition for miRNA that regulate mRNA translation through sponging miRNAs. Identification of various oncogenic lncRNAs and their multiple roles in brain cancers making them potential candidates for use as glioma diagnostic, prognostic, and therapeutic targets in the future. This study highlighted multiple oncogenic lncRNAs and classified them into different signaling pathways based on the regulated target genes in glioblastoma.