Developmental Neurobiology最新文献

{"title":"Exploring the Role of NLRP3 in Neurodegeneration: Cutting-Edge Therapeutic Strategies and Inhibitors","authors":"Mohammed Ahmed Mustafa,&nbsp;Pooja Bansal,&nbsp;MS Pallavi,&nbsp;Rajashree Panigrahi,&nbsp;Deepak Nathiya,&nbsp;Sachin Kumar,&nbsp;Shaker Al-Hasnaawei,&nbsp;Ashish Singh Chauhan,&nbsp;Siya Singla","doi":"10.1002/dneu.22982","DOIUrl":"https://doi.org/10.1002/dneu.22982","url":null,"abstract":"<div>\u0000 \u0000 <p>Inflammasomes, particularly the NLRP3 inflammasome, play a pivotal role in mediating neuroinflammation in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Huntington's disease (HD). Recent findings indicate that the activation of the NLRP3 inflammasome in microglia and astrocytes triggers the release of pro-inflammatory cytokines, including IL-1β and IL-18, which contribute to chronic inflammation and neuronal damage. This process accelerates neurodegeneration and exacerbates disease progression. Misfolded protein aggregates, mitochondrial dysfunction, and oxidative stress are key factors in the pathological activation of the NLRP3 inflammasome in these diseases. Recent studies have highlighted that targeting the NLRP3 inflammasome, either through direct inhibitors like MCC950 or natural compounds such as oridonin and β-hydroxybutyrate, shows promise in mitigating neuroinflammation and protecting neuronal integrity. These inhibitors have demonstrated neuroprotective effects in animal models of AD, PD, and MS, presenting a new therapeutic approach for halting disease progression. However, the complexity of NLRP3 regulation requires further investigation to balance its inflammatory and protective roles. This review examines the recent advancements in NLRP3 inflammasome research and discusses potential strategies for modulating inflammasome activity to slow or prevent the progression of neurodegenerative diseases.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220144","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":"GATA Transcription Factors: A Cross-Road for Erythropoiesis, Neurodevelopment, and Synucleinopathies","authors":"Francesco Bellomi,&nbsp;Claudia Caturano,&nbsp;Viola Velardi,&nbsp;Romina Mancinelli,&nbsp;Simone Carotti,&nbsp;Giorgio Vivacqua,&nbsp;Francesca Arciprete,&nbsp;Maria Zingariello","doi":"10.1002/dneu.22975","DOIUrl":"https://doi.org/10.1002/dneu.22975","url":null,"abstract":"<p>Alpha-synuclein (α-syn), a 140 amino acid protein, is abundantly expressed in the central nervous system (CNS) and in the erythrocytes, playing a pivotal role in the pathogenesis of Parkinson's disease (PD) and other synucleinopathies. Among the GATA family transcription factors (TFs), GATA1 and GATA2 regulate the meg-erythrocytic differentiation starting from the hematopoietic stem cell. In erythropoiesis, the GATA1-2 switching regulates the expression of the α-syn gene (SNCA) in the erythrocytes, which is essential for iron metabolism and membrane stability. Abnormalities in α-syn regulation alter erythrocytic function, possibly contributing to pathological mechanisms of different synucleinopathies. In CNS, during neuronal development, GATA2 confirms its role in stemness by maintaining the ventral neuronal progenitors and also leading GABAergic, serotoninergic, and sympathetic neuron differentiation. Therefore, although no evidence is reported regarding a direct role of GATA1 in neuronal lineage, GATA3 recruitment and activation are essential for the maturation of specific neuronal subtypes. This short scope review explores the bridging role of GATA TFs in erythropoiesis and neuronal development, highlighting their involvement in α-syn regulation, as well as their potential role in the pathogenesis of synucleinopathies.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.22975","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220139","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}

{"title":"Maternal Stress and Maternal Microbiome Manipulations Remodel Offspring Medial Prefrontal Cortex in a Sex-Dependent Manner","authors":"Luke Gohmann,&nbsp;Jessica A. Cusick,&nbsp;Gregory E. Demas,&nbsp;Cara L. Wellman","doi":"10.1002/dneu.22971","DOIUrl":"https://doi.org/10.1002/dneu.22971","url":null,"abstract":"<div>\u0000 \u0000 <p>Maternal stress and disruptions of the maternal microbiome during development can have profound organizational effects on the brain and behavior of offspring. We have previously demonstrated that these manipulations have marked, sex-dependent effects on aggressive behavior in Siberian hamsters, <i>Phodopus sungorus</i>. Given that the prelimbic cortex is sensitive to stress and may play a role in modulating social behaviors, here we investigated how maternal stress and disruption of the microbiome during pregnancy may affect the development of the prelimbic cortex in offspring. Pregnant hamsters were exposed to either a broad-spectrum antibiotic, social stress, combined treatments, or no manipulation (i.e., control). Adult offspring (PND 107–115) were euthanized, brains were stained using Golgi histology, and apical and basilar dendritic lengths of pyramidal cells in the prelimbic cortex were quantified. Our data indicate that maternal stress and microbiome manipulation have a sex-dependent effect on offspring dendritic morphology. Maternal stress increased apical dendritic length in female but not male offspring relative to controls. However, the combination of maternal stress and maternal antibiotics ameliorated the effect of stress alone. Thus, maternal stress and disruption of the microbiome interact to produce lasting changes in the prefrontal cortex of female offspring. Such changes may contribute to the behavioral effects of these manipulations.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191145","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":"Effects of the Missense Variants on Complete Phenotype and Splicing Variant on Severe Growth Retardation in the BPTF Gene","authors":"Gül Ünsel-Bolat,&nbsp;Hamide Betul Gerik-Celebi,&nbsp;Betül Diler Durgut,&nbsp;Ayberk Türkyılmaz,&nbsp;Hilmi Bolat","doi":"10.1002/dneu.22970","DOIUrl":"https://doi.org/10.1002/dneu.22970","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL, OMIM no #617755) is an ultra-rare syndrome associated with heterozygous pathogenic variants in the <i>BPTF</i> gene. Haploinsufficiency of the <i>BPTF</i> gene, a chromatin remodeling gene that is related to epigenetic modification, is the cause of this disease.</p>\u0000 \u0000 <p><i>BPTF</i> gene variants were detected using whole-exome sequencing. Family segregation analysis was performed using sanger sequencing.</p>\u0000 \u0000 <p>This study reported three variants, c.2812+1G&gt;C, c.6022G&gt;A, and c.6416G&gt;A in the <i>BPTF</i> gene. The variations of the c.6022G&gt;A and c.2812+1G&gt;C have not been previously reported in variant types observed at the <i>BPTF</i> gene in sources including Genome Aggregation Database (gnomAD), Leiden Open Variation Database (LOVD), Human Gene Mutation Database (HGMD), and ClinVar.</p>\u0000 \u0000 <p>We detected two novel missense variants in patients presenting all phenotypic characteristics of the <i>BPTF</i>-related NEDDFL syndrome severely, including severe ID, distinctive facial features, and anomalies of the hands and feet. Additionally, all four of our cases in this study had distal limb abnormalities such as syndactyly and clinodactyly that accompany severe intellectual disability. We suggest that distal limb abnormalities associated with the <i>BPTF</i> gene may accompany a more severe diagnosis of intellectual disability. Also, growth retardation may be more severe, especially for the cases with splicing variants of the <i>BPTF</i> gene variants.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.22970","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135810","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}

{"title":"Mangrove-Crab Blood Cells Proliferate In Vitro and Display Neuronal Proteins Following Pituitary-Extract Stimulus","authors":"Inês Júlia Ribas Wajsenzon,&nbsp;Isadora Santos de Abreu,&nbsp;Carlos Augusto Borges de Andrade Gomes,&nbsp;Wagner Antônio Barbosa da Silva,&nbsp;Adriano Biancalana,&nbsp;Elizabeth Giestal-de-Araujo,&nbsp;Silvana Allodi","doi":"10.1002/dneu.22972","DOIUrl":"https://doi.org/10.1002/dneu.22972","url":null,"abstract":"<p>In this study we propose a cell-culture protocol to better comprehend the involvement of immune/blood cells (hemocytes) in the adult neurogenesis of crustaceans. We examined whether the hemocytes of the crab <i>Ucides cordatus</i> may develop into neural cells in response to an in vitro stimulus. The experiments involved two steps. First, we selected an appropriate substrate for use in the culture medium. Hemocytes proliferated and differentiated most on poly-<span>d</span>-lysine. Second, we added pituitary extract to the poly-<span>d</span>-lysine-coated culture in order to determine the cell types into which hemocytes differentiated. This supplement was chosen due to its mitogenic and cell-differentiation properties. Using cell type-specific antibodies (anti-GFAP, anti-vimentin, anti-beta III Tubulin, and anti-NeuN), we were able to identify putative neural progenitors. This showed that upon stimulation, hemocytes have mitotic activity and can display neural precursor proteins. In contrast to the protocols commonly used for vertebrate cell cultures, the protocol used here proved, for the first time, to be capable of stimulating crustacean blood cells to grow. This method also offers a basis for cultivating crustacean blood cells for various purposes, such as the study of adult neurogenesis.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.22972","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135811","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}

{"title":"Cannabis Oil Protects Against Valproic Acid–Induced Autism Spectrum Disorder by Reducing Oxidative Stress","authors":"Faiza Ali,&nbsp;Adeeb Shehzad,&nbsp;Raheem Shahzad,&nbsp;Salman Khan,&nbsp;Luay Rashan,&nbsp;Muhammad Taha","doi":"10.1002/dneu.22969","DOIUrl":"https://doi.org/10.1002/dneu.22969","url":null,"abstract":"<div>\u0000 \u0000 <p>Autism spectrum disorder (ASD) is characterized by persistent problems in speech, social interaction, restricted and repetitive behavior patterns, lack of interest, and intellectual disabilities. Currently, there is no effective treatment available for the core symptoms of ASD. Among various treatments, herbal pharmacological treatments have shown promising results with fewer side effects, especially cannabidiol (CBD) treatment for the core symptoms and co-morbidities of ASD. The current study was performed to explore the therapeutic potential of CBD oil supplementation against the valproic acid (VPA)-induced autism mouse model. The autism mouse model was developed by exposing albino BALB/c mouse fetuses to VPA (600 mg/kg) on gestational day 13. On postnatal day (PND)-21, the male pups from both control and diseased groups were further divided into the following treatment groups: (I) control saline group, (II) VPA-exposed group, (III) VPA + CBD oil (100 mg/kg/day/orally) group, and (IV) standard group of VPA + risperidone (RISP) (0.5 mg/kg/day/orally) for 3 consecutive weeks. VPA mice displayed autistic behaviors upon delivery, such as increased anxiety levels, delayed response to painful stimuli, and impaired social interaction. VPA mice also showed depletion of glutathione and other antioxidant levels. CBD oil improved these dysfunctions, as seen through biochemical analysis and morphological staining of the hippocampal region, prefrontal cortex, and Purkinje cells. These findings showed that CBD oil treatment significantly improved behavioral abnormalities and lowered the oxidative stress in the autistic mouse model by acting as an antioxidant.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085211","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":"Mature and Juvenile Neuromuscular Plasticity in Response to Unloading","authors":"Michael R. Deschenes,&nbsp;Max Rackley,&nbsp;Sophie Fernandez,&nbsp;Megan Heidebrecht","doi":"10.1002/dneu.22966","DOIUrl":"https://doi.org/10.1002/dneu.22966","url":null,"abstract":"<p>The neuromuscular junction (NMJ) is the synapse that enables the requisite electrical communication between the motor nervous system and the myofibers that respond to such electrical stimulation with movement and force development. Changes in an NMJ's normal activity pattern have been demonstrated to remodel both the synapse and the myofibers that comprise the NMJ. Significant amounts of research have been devoted to the study of aging on the neuromuscular system. Far less, however, has been focused on revealing the effects of reduced activity on the NMJ and myofibers comprising juvenile neuromuscular systems. In the present investigation, the consequences of decreased activity imposed by muscle unloading (UL) via hindlimb suspension for 2 weeks (a period known to induce muscle remodeling) were examined in both young adult, that is, mature (8 mo), and juvenile (3 mo) neuromuscular systems. In total, 4 treatment groups comprised of 10 animals (Juvenile-Control, Juvenile-Unloaded, Mature-Control, and Mature-Unloaded) were studied. Immunofluorescent procedures, coupled with confocal microscopy, were used to quantify remodeling of both the pre- and postsynaptic features of NMJs, as well as assessing the myofiber profiles of the soleus muscles housing the NMJs of interest. Results of ANOVA procedures revealed that there were significant (<i>p</i> &lt; 0.05) main effects for both treatment, whereby UL consistently led to expanded size of the NMJ, and Age where expanded NMJ dimensions were consistently linked with mature compared to juvenile neuromuscular systems. Moreover, only sporadically was interaction between the main effects of Age and Treatment noted. Importantly, one variable that remained impressively resistant to the effects of both Age and Treatment was the critical parameter of pre- to postsynaptic coupling suggesting stability in effective communication at the NMJ throughout the lifespan and despite changes in activity patterns. The data presented here suggest that further inquiry must be performed regarding disuse-related plasticity of the neuromuscular system in adolescent individuals as those individuals regularly suffer injuries resulting in periods of muscle UL.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.22966","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919351","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}

{"title":"Distinct Developmental Programs Displayed by the Xenopus Tadpole Accessory Optic System and Retinotectal Projection","authors":"Uwemedimo G. Udoh,&nbsp;Kaiyuan Zheng,&nbsp;John R. Bruno,&nbsp;Jasper E. Hunt,&nbsp;Kara G. Pratt","doi":"10.1002/dneu.22968","DOIUrl":"https://doi.org/10.1002/dneu.22968","url":null,"abstract":"<div>\u0000 \u0000 <p>The retinotectal projection, the direct synapse between retinal ganglion cells (RGCs) of the eye and tectal neurons of the optic tectum, is a major component of the amphibian visual system. A model of circuit formation, this projection has been studied in detail. There are, however, other retinorecipient targets that also comprise the amphibian visual system such as the pretectum and ventral midbrain tegmentum. Understanding how these other components of the visual system form and function will lead to a more comprehensive understanding of how the visual system, as a whole, assembles and functions. Toward this aim, here we describe the functional development of the <i>Xenopus</i> tadpole accessory optic system (AOS), a direct synaptic connection between RGC axons and the basal optic nucleus of the midbrain tegmentum. The AOS is highly conserved across vertebrates. It functions as the sensory side of the optokinetic and optomotor reflexes, compensatory eye and body movements, respectively, that stabilize the visual scene as the organism moves through it. Using an isolated brain preparation and whole-cell electrophysiological approaches, we compared the development of the AOS and retinotectal projection. We found that these two retinofugal projections display distinct developmental programs, which appear to mirror their different functions. Retinotectal synapses moved through a dynamic phase of previously described NMDA receptor-dependent refinement, a process that is known to sharpen the retinotopic map and thereby visual acuity. In contrast, the AOS synapse appeared more stable and activity independent across development, indicative of a hardwired circuit, built to support reflexive optic behaviors.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919352","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":"Elevated Serum Histamine N-Methyltransferase Levels Are Associated With the Pathophysiology of Major Depressive Disorder: A Case–Control Study","authors":"Mariya Akter,&nbsp;Dibbo Protim Ghosh,&nbsp;Toha Tasnem,&nbsp;Tanvir Ahmed,&nbsp;Md. Aminul Haque,&nbsp;Md. Siddiqul Islam,&nbsp;Md. Rabiul Islam","doi":"10.1002/dneu.22967","DOIUrl":"https://doi.org/10.1002/dneu.22967","url":null,"abstract":"<div>\u0000 \u0000 <p>Major depressive disorder (MDD) is a common neuropsychiatric disorder with persistent low mood, feelings of weakness, and a lack of interestin daily tasks. Histamine N-methyltransferase (HNMT) protein is involved in the inactivation process of histamine in human physiology. Here, we aimed to assess the role of HNMT in the pathophysiology and development of MDD. This case–control study included 56 MDD patients and 32 healthy controls (HCs) by matching age, sex, body mass index (BMI), and other sociodemographic characteristics. A clinical psychiatrist assessed the MDD patients and HCs according to the DSM-5 criteria. We used the Ham-D scale in evaluating the severity of depressive symptoms. We used ELISA kits to estimate serum HNMT levels. We observed elevated serum HNMT concentration in MDD patients (29.25 ± 5.34 pg/ml) compared with HCs (23.13 ± 2.10 pg/ml). Serum HNMT levels and Ham-D scores are positively correlated with each other in MDD patients (<i>r</i> = 0.632, <i>p</i> &lt; 0.001). Also, the receiver operating characteristic curve analysis illustrated a significant diagnostic value for HNMT with the area under the curve (AUC = 0.916) at <i>p</i> &lt; 0.001. The promising findings from this study anticipate that the elevated serum levels of HNMT may be associated with the pathophysiology and mechanism of MDD. We recommend further interventional studies to produce more precise and accurate results on this biomarker in depression.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897030","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 Rare Syndrome Aicardi–Goutières 4: A Case Report and Literature Review","authors":"Hilal Aydin,&nbsp;Hilmi Bolat","doi":"10.1002/dneu.22965","DOIUrl":"https://doi.org/10.1002/dneu.22965","url":null,"abstract":"<p>Aicardi–Goutières syndrome (AGS) is a genetically heterogeneous type of interferonopathy resulting from defects in the processing or sensing of nucleic acids. The AGS phenotype encompasses a broad range of neurological and non-neurological findings. It presents with a congenital or subacute onset, manifesting as microcephaly, spasticity, dystonia, seizures, cortical blindness, and psychomotor retardation in the first year of life. The radiological and laboratory findings of AGS are generally accompanied by intracranial calcification, white matter abnormalities, cerebral atrophy, and cerebrospinal fluid lymphocytic pleocytosis. A case diagnosed as AGS type 4 among patients presenting to the Balikesir University Medical Faculty pediatric neurology clinic, Türkiye, between August 1, 2024, and February 1, 2025, and undergoing genetic testing was included in the study. The patient exhibited a coarse facial appearance, a low ear line, scoliosis, contractures in the upper and lower extremities, hyperactive deep tendon reflexes, an equivocal Babinski response, and upper and lower extremity muscle strength of 3/5. The patient was started on levetiracetam at 20 mg/kg in two doses for epilepsy. Whole exome sequencing revealed a homozygous pathogenic variant in <i>RNASEH2A</i>. Parental genetic analyses for the targeted variant were heterozygous. In conclusion, the diagnosis of AGS relies on clinical characteristics and genetic testing. Basic neurological characteristics include developmental delay, dystonia, microcephaly, brain calcification, and leukodystrophy. Although data concerning genotype-phenotype in AGS type 4 have been reported in the literature, these are still limited.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.22965","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143861457","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}