Neurogenetics最新文献

{"title":"Predicting high-risk clinical missense variants of SMARCB1 in rare neurogenetic disorder schwannomatosis (nerve tumor) through sequence, structure, and molecular dynamics analyses.","authors":"Mitesh Patel, Reem Binsuwaidan, Malvi Surti, Nawaf Alshammari, Angum M M Ibrahim, Mohd Adnan","doi":"10.1007/s10048-025-00812-z","DOIUrl":"10.1007/s10048-025-00812-z","url":null,"abstract":"<p><p>The SMARCB1 gene codes for a key element of the SWI/SNF chromatin-modifying complex, which plays a vital role in controlling gene expression by modifying chromatin architecture. Alterations in SMARCB1 have been linked to several neurological disabilities, including schwannomatosis, a condition marked by the formation of numerous benign tumors affecting the nerve sheaths. Present study explore the effects of nonsynonymous single nucleotide polymorphisms (nsSNPs) within the SMARCB1 gene on its protein structure and functionality. We utilized both sequence-based and structure-oriented predictive models, followed by molecular dynamics simulations to examine their influence on the stability of protein and dynamic behaviour. The study focused on three key mutations: R60S, R190W, and I237M. The R190W mutation emerged as particularly significant, leading to increased protein compactness and stability due to enhanced hydrophobic interactions, although conformational flexibility was reduced. The R60S mutation was associated with destabilization of the protein structure, increasing solvent exposure and reducing hydrogen bond stability, potentially impairing the protein's function. The I237M mutation had a relatively mild impact, with only subtle changes observed in protein dynamics. These findings highlight the diverse impacts of different nsSNPs on SMARCB1, with the potential to contribute to various pathologies, including Schwannomatosis and other related disorders. This study highlights the necessity for additional experimental testing to confirm these computational findings and gain a deeper understanding of the molecular processes through which these mutations contribute to disease. The present comprehensive approach provides significant knowledge regarding the connection between SMARCB1 structure and function, providing the groundwork for potential therapeutic strategies targeting these key mutations.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"31"},"PeriodicalIF":1.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"20 years of ROBO3-related horizontal gaze palsy with progressive scoliosis: a mini-review.","authors":"Ehab Y Harahsheh, Lauren E Moxley, Matu Al-Amin, Sonia Sabrowsky, Adnan Deniz, Mayowa Osundiji","doi":"10.1007/s10048-025-00811-0","DOIUrl":"10.1007/s10048-025-00811-0","url":null,"abstract":"<p><p>ROBO3 is a member of the Roundabout (ROBO) gene family of evolutionarily conserved guidance receptors, which plays crucial roles in axon crossing of the CNS midline. In 2004, pathogenic variants in ROBO3 were first linked to Horizontal Gaze Palsy with Progressive Scoliosis type 1 [HGPPS1 (OMIM # 607313)], an autosomal recessive disorder that is characterized by failure of the corticospinal and somatosensory axon tracts to decussate in the medulla. Hitherto, over 60 ROBO3 pathogenic (or likely pathogenic) variants associated with HGPPS1 have been described in almost 100 patients. With the 20-year milestone, this minireview underscores the growing opportunities to improve the current understanding of the spectrum of HGPPS1 phenotype and ROBO3 genotypes. The increasing need for translational studies that can pave the way for improved clinical management of ROBO3-related disorders is also highlighted.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"30"},"PeriodicalIF":1.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ABCB1 c.3435 C > T (rs1045642) as a biomarker for carbamazepine efficacy and toxicity in Algerian patients with epilepsy: initial findings report.","authors":"Rachda Riffi, Wefa Boughrara, Meriem Samia Aberkane, Wassila Ilias, Mohamed Sofiane Bouchetara, Amel Alioua Berrebbah, Fatma Belhoucine, Amina Chentouf","doi":"10.1007/s10048-025-00807-w","DOIUrl":"10.1007/s10048-025-00807-w","url":null,"abstract":"<p><p>Epilepsy is among the most prevalent serious neurological disorders, affecting over 70 million people worldwide, in Algeria, the prevalence of epilepsy was estimated to be eight times more common. Carbamazepine is frequently the first-line treatment, making early prediction of patient response essential for personalized care. This approach helps reduce adverse effects and healthcare costs, while enhancing patient outcomes. This study aims to explore the link between the ABCB1 c.3435C > T genetic variation and Carbamazepine resistance and toxicity in Algerian patients with epilepsy, with a focus on the impact of genetic variations on Carbamazepine plasma concentrations and treatment outcomes. Ninety-eight Algerian patients with epilepsy were recruited and categorized as either drug-responsive or drug-resistant based on their clinical response to CBZ treatment. Genotyping of the ABCB1 c.3435 C > T polymorphism was performed using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method, and CBZ plasma levels were measured to assess its effect on metabolism. Clinical data, including drug response, therapy type, and adverse drug reactions (ADRs), were collected and analyzed. For the statistical analysis we used chi-squared tests and Exact Fisher's for corrections. Our findings show no significant association between the ABCB1 c.3435C > T genotypes with carbamazepine resistance (p = 0,1) nor incidence of adverse reactions. This polymorphism also indicated no statistically significant link with Carbamazepine plasma levels. The sample size in this study might be limitation; therefore, expanded investigations on Algerian population are needed. Although this study indicates no significant correlation of the ABCB1 c.3435C > T polymorphism with influencing CBZ Pharmacoresistance and therapeutic outcomes, larger-scale-studies are required to confirm these results and assess their reliability.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"29"},"PeriodicalIF":1.6,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early-onset Parkinson's disease in a patient with a rare homozygous pathogenic GBA1 variant and no Gaucher disease symptoms.","authors":"Juliana Cordovil Cotrin, Rafael Mina Piergiorge, Andressa Pereira Gonçalves, Mariana Spitz, Alexandra Lehmkuhl Gerber, Ana Paula de Campos Guimarães, Ana Tereza Ribeiro Vasconcelos, Cíntia Barros Santos-Rebouças","doi":"10.1007/s10048-025-00810-1","DOIUrl":"10.1007/s10048-025-00810-1","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a multifaceted neurodegenerative disorder with both non-motor and motor symptoms. Variants in the glucosylceramidase beta 1 (GBA1) gene are the strongest genetic risk factor for PD, while homozygous or compound heterozygous variants in this gene classically cause Gaucher disease (GD). This study presents an early-onset PD patient with a homozygous GBA1 deletion. Whole-exome sequencing (WES) was performed, and the identified variant was validated via Sanger sequencing. The variant was classified according to ACMG guidelines and ClinGen updates. The patient, a Brazilian female of mixed ethnicity, exhibited the full spectrum of classical motor and non-motor PD symptoms without evident hallmarks of GD. The identified homozygous GBA1 variant (NM_000157.4:c.222_224del; p.T75del; rs761621516) has a very low global allele frequency (0.00003284) and is associated with reduced enzymatic activity. This variant exhibits a founder effect among individuals of African descent. This case highlights an intricate genotype-phenotype landscape for GBA1 variants, underscoring the role of homozygous GBA1 variants in PD pathogenesis.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"28"},"PeriodicalIF":1.6,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of critical genes and drug repurposing targets in entorhinal cortex of Alzheimer's disease.","authors":"Arghavan Hosseinpouri, Khadijeh Sadegh, Zeinab Zarei-Behjani, Zeinab Dehghan, Reza Karbalaei","doi":"10.1007/s10048-025-00806-x","DOIUrl":"10.1007/s10048-025-00806-x","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a slow brain degeneration disorder in which the accumulation of beta-amyloid precursor plaque and an intracellular neurofibrillary tangle of hyper-phosphorylated tau proteins in the brain have been implicated in neurodegeneration. In this study, we identified the most important genes that are unique and sensitive in the entorhinal region of the brain to target AD effectively. At first, microarrays data are selected and constructed protein-protein interaction network (PPIN) and gene regulatory network (GRN) from differentially expressed genes (DEGs) using Cytoscape software. Then, networks analysis was performed to determine hubs, bottlenecks, clusters, and signaling pathways in AD. Finally, critical genes were selected as targets for repurposing drugs. Analyzing the constructed PPIN and GRN identified CD44, ELF1, HSP90AB1, NOC4L, BYSL, RRP7A, SLC17A6, and RUVBL2 as critical genes that are dysregulated in the entorhinal region of AD suffering patients. The functional enrichment analysis revealed that DEG nodes are involved in the synaptic vesicle cycle, glutamatergic synapse, PI3K-Akt signaling pathway, retrograde endocannabinoid signaling, endocrine and other factor-regulated calcium reabsorption, ribosome biogenesis in eukaryotes, and nicotine addiction. Gentamicin, isoproterenol, and tumor necrosis factor are repurposing new drugs that target CD44, which plays an important role in the development of AD. Following our model validation using the existing experimental data, our model based on previous experimental reports suggested critical molecules and candidate drugs involved in AD for further investigations in vitro and in vivo.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"27"},"PeriodicalIF":1.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: Impact of flexible assertive community treatment model (FACT) on community rehabilitation of schizophrenia in Southern China.","authors":"Yinglin Zhao, Shaoxiong Zheng, Handi Zhang, Yinnan Zhang, Zidong Wang, Qingjun Huang","doi":"10.1007/s10048-025-00809-8","DOIUrl":"https://doi.org/10.1007/s10048-025-00809-8","url":null,"abstract":"","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"26"},"PeriodicalIF":1.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and expressional insights into the association of TRAPPC10 variants with neurodevelopmental disorders.","authors":"Peng-Yu Wang, Wen-Hui Liu, Yu-Jie Gu, Sheng Luo","doi":"10.1007/s10048-025-00804-z","DOIUrl":"https://doi.org/10.1007/s10048-025-00804-z","url":null,"abstract":"","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"25"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Gene-gene interaction network analysis indicates CNTN2 is a candidate gene for idiopathic generalized epilepsy.","authors":"Zhi-Jian Lin, Jun-Wei He, Sheng-Yin Zhu, Li-Hong Xue, Jian-Feng Zheng, Li-Qin Zheng, Bi-Xia Huang, Guo-Zhang Chen, Peng-Xing Lin","doi":"10.1007/s10048-025-00802-1","DOIUrl":"https://doi.org/10.1007/s10048-025-00802-1","url":null,"abstract":"","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"24"},"PeriodicalIF":1.6,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic variability in progressive encephalopathy with brain atrophy and thin corpus callosum: insights from two families.","authors":"Busra Aynekin, Sinan Akbaş, Ayten Gulec, Ummu Gulsum Ozgul Gumus, Abdullah Emre Guner, Stephanie Efthymiou, Henry Houlden, Gözde Yesil Sayın, Huseyin Per","doi":"10.1007/s10048-025-00799-7","DOIUrl":"10.1007/s10048-025-00799-7","url":null,"abstract":"<p><p>The cytoskeleton, composed of microtubules, intermediate filaments and actin filaments is vital for various cellular functions, particularly within the nervous system, where microtubules play a key role in intracellular transport, cell morphology, and synaptic plasticity. Tubulin-specific chaperones, including tubulin folding cofactors (TBCA, TBCB, TBCC, TBCD, TBCE), assist in the proper formation of α/β-tubulin heterodimers, essential for microtubule stability. Pathogenic variants in these chaperone-encoding genes, especially TBCD, have been linked to Progressive Encephalopathy with Brain Atrophy and Thin Corpus Callosum (PEBAT, OMIM #604,649), a severe neurodevelopmental disorder. We report three cases from two consanguineous families with varying clinical presentations of PEBAT syndrome due to homozygous pathogenic variants in the TBCD. In Family 1, two siblings (F1C1 and F1C2) harboring the homozygous c.2314C > T, p.(Arg772Cys) variant exhibited severe neurodevelopmental regression, spastic tetraplegia, seizures, and brain atrophy. In contrast, Family 2, Case 3 (F2C3), with the homozygous c.230A > G, p.(His77Arg) variant, presented a milder phenotype, including absence seizures, slight developmental delay, and less pronounced neuroanatomical abnormalities. These findings contribute to the expanding phenotypic spectrum of PEBAT and suggesting that modifier genes or epigenetic factors may influence disease severity.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"23"},"PeriodicalIF":1.6,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The molecular mechanism of nitric oxide in memory consolidation and its role in the pathogenesis of memory-related disorders.","authors":"Zainab I Bahdar, Ejlal Abu-El-Rub, Rawan Almazari, Ayman Alzu'bi, Raed M Al-Zoubi","doi":"10.1007/s10048-025-00803-0","DOIUrl":"10.1007/s10048-025-00803-0","url":null,"abstract":"<p><p>Memory is a dynamic process of encoding, storing, and retrieving information. It includes sensory, short-term, and long-term memory, each with unique characteristics. Nitric oxide (NO) is a biological messenger synthesized on demand by neuronal nitric oxide synthase (nNOS) through a biochemical process initiated by glutamate binding to NMDA receptors, causing membrane depolarization and calcium influx. NO is known to regulate many signaling pathways including those related to memory consolidation. To throw light on the precise molecular mechanism of nitric oxide (NO) in memory consolidation and the possibility of targeting NO pathways as a therapeutic approach to scale down cognitive impairments. We conducted a search of the PubMed MEDLINE database, maintained by the US National Library of Medicine. The search strategy utilized Medical Subject Headings (MeSH) terms, including \"nitric oxide and memory,\" \"nitric oxide synthesis in the brain,\" \"nitric oxide and Alzheimer's,\" \"nitric oxide and Parkinson's,\" and \"nitric oxide, neurodegenerative disorders, and psychiatric disorders.\" Additionally, relevant keywords such as \"nitric oxide,\" \"memory,\" and \"cognitive disorders\" were employed. We included the most recent preclinical and clinical studies pertinent to the review topic and limited the selection to articles published in English. NO exerts its role in memory consolidation by diffusing between neurons to promote synaptic plasticity, especially long-term potentiation (LTP). It acts as a retrograde messenger, neurotransmitter release modulator, and synaptic protein modifier. The dysregulation of NO balance in the brain can contribute to the pathogenesis of various neurodegenerative diseases, particularly Alzheimer's, Parkinson's, and psychiatric disorders. The disturbance in NO signaling is strongly correlated with synaptic signaling dysfunction and oxidative stress. NO plays a fundamental role in memory consolidation, and its dysregulation contributes to cognitive impairment-a hallmark of numerous neurodegenerative and psychiatric disorders. Future research should aim to deepen our understanding of the mechanisms underlying NO's involvement in memory consolidation and to explore therapeutic strategies targeting the NO pathway to mitigate cognitive decline in affected individuals.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"22"},"PeriodicalIF":1.6,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}