Developmental Neurobiology最新文献

{"title":"Neuron-Derived Extracellular Vesicles: Emerging Biomarkers and Functional Mediators in Alzheimer's Disease, With Comparative Insights Into Neurodevelopment and Aging","authors":"Ceren Perihan Gonul,&nbsp;Bilge Karacicek,&nbsp;Sermin Genc","doi":"10.1002/dneu.22984","DOIUrl":"https://doi.org/10.1002/dneu.22984","url":null,"abstract":"<p>Alzheimer's disease (AD) is one of the most common neurodegenerative disorders characterized by the accumulation of amyloid-β (Aβ) peptide and phosphorylated tau protein in the brain. Despite intensive efforts, early diagnosis and monitoring of AD remain challenging due to the lack of reliable biomarkers that can detect the disease in its preclinical stages. As a result, there exists a requirement for novel approaches to the diagnosis and treatment of the disease. Extracellular vesicles provide the transfer of Aβ peptides and tau proteins between the cells and participates in the spreading/propagation of disease pathology. Neuron-derived extracellular vesicles (NDEVs) that are found in plasma have emerged as promising candidates, especially for biomarker studies on neurodegenerative diseases because they are reachable and comparable with cerebrospinal fluid (CSF) studies. In addition to known proteins, synaptic proteins, transcription factors, or microRNAs have been suggested as new biomarkers, aiming to help differential or early diagnosis. Beyond their involvement in AD pathology, NDEVs also play essential roles in neurodevelopment and aging by mediating cell-to-cell communication and regulating processes such as synaptic formation, neuronal differentiation, and neuroinflammation. Age-related alterations in EV composition and secretion may contribute to the decline in neuroplasticity, thereby increasing susceptibility to neurodegenerative diseases like AD. Several challenges such as heterogeneous isolation of NDEVs limit the widespread clinical application of them as biomarkers for AD. Furthermore, the lack of standardized protocols for vesicle isolation and molecular analysis poses a barrier to reproducibility and clinical validation. The aim of this review is to elucidate the role of NDEVs in AD pathogenesis in comparison with their functions in neurodevelopment and aging, evaluate their potential as biomarkers for early diagnosis, while addressing the challenges in their isolation, characterization, and clinical application.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.22984","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264616","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":"Developmental Disturbances in Animal Models of Autism Spectrum Disorder","authors":"Kristof Laszlo,&nbsp;Zuzana Bacova,&nbsp;Dora Zelena,&nbsp;Jan Bakos","doi":"10.1002/dneu.22977","DOIUrl":"https://doi.org/10.1002/dneu.22977","url":null,"abstract":"<p>Although the early signs of autism spectrum disorder (ASD) are widely studied, the significant ambiguity and heterogeneity in symptoms require the comparison of available models, approaches, and the search for common denominators and key indicators. Early ASD symptoms in animal models include impaired somatic development (e.g., delayed eye opening), alterations in primitive motor reflexes, disrupted sensory function as well as communication deficits, such as reduced ultrasonic vocalization. This review aims to summarize early ASD-related symptoms based on studies involving transgenic or neurotoxic rodent models (postnatal days 1–21) and to compare these with human resemblance. The key brain areas (subventricular zone, cortex, hippocampus, cerebellum, etc.) as well as relevant neurotransmitter systems (GABA-glutamate imbalance, developmental GABA shift, serotonin, dopamine, oxytocin [OT], etc.) were identified as potential targets for intervention. OT, although a promising candidate, exemplifies the translational challenges inherent in ASD research. Therefore, it is recommended to monitor a wide range of behavioral signs simultaneously and employ diverse models (e.g., genetic, developmental, environmental, or combination) in preclinical studies to more accurately reflect the complexity of the disorder.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.22977","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256467","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":"Characterization of Neural Stem Cells of the Human Embryonic Fetus Across Regions of the Central Nervous System and Through Standard Gestation Period Assessments","authors":"Yu Mi Park,&nbsp;Hyun Young Kim","doi":"10.1002/dneu.22980","DOIUrl":"https://doi.org/10.1002/dneu.22980","url":null,"abstract":"<div>\u0000 \u0000 <p>In this study, the characteristics of human embryonic fetuses aborted due to ectopic pregnancy were preliminarily evaluated on the basis of gestational age (GA), crown-rump - length (CRL), and their carnegie stage (CS). Further, we attempted to establish the human neural stem cells (NSCs) and neural progenitor cells (NSCs/NPCs) by separating them into corresponding areas of the brain and spinal cord (SC), as much as was visually distinguishable, considering that the distribution of neurons differs across different brain areas. We successfully isolated and cultured NSCs/NPCs from regional brain and SC tissues of human embryonic fetuses. The isolated NSCs/NPCs not only exhibited the ability to self-proliferate but also had the potential to differentiate into neurons, motor neurons, and glial cells. We confirmed that the isolated Sox2 and Nestin expression in the NSCs/NPCs showed strong neural stemness and further verified how the expression markers, MAP-2, β-tubulin III(TuJ1), ChAT, HB9, GFAP, and Olig-2, could be harnessed while differentiating to neurons, motor neurons, and glial cells. NSCs with varying GA, CS, and CRLs were found to be capable of producing all neural lineages of neurons, astrocytes, and oligodendrocytes. We could completely differentiate them to neurons, motor neurons, and oligodendrocytes, except for a difference noted with astrocyte differentiation. This study provides vital experimental data for cell and gene therapy.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256414","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 Inactivation of the Serotonin Transporter Dysregulates Expression of Neurotransmission Genes and Genome-Wide DNA Methylation Levels in the Medial Prefrontal Cortex of Male Rats During Postnatal Development","authors":"Yvet Kroeze,&nbsp;Martin Oti,&nbsp;Roel H. M. Cooijmans,&nbsp;Ellen van Beusekom,&nbsp;Leonie I. Kroeze,&nbsp;Anthonieke Middelman,&nbsp;Hans van Bokhoven,&nbsp;Sharon M. Kolk,&nbsp;Judith R. Homberg,&nbsp;Huiqing Zhou","doi":"10.1002/dneu.22973","DOIUrl":"https://doi.org/10.1002/dneu.22973","url":null,"abstract":"<p>Reduced expression of the serotonin transporter (5-hydroxytryptamine transporter, 5-HTT) in early life has been associated with a delay in postnatal brain development and endophenotypes of a variety of neuropsychiatric and neurodevelopmental disorders in adolescence and adulthood. How a reduction in functional 5-HTT can disrupt neurodevelopment is still largely unknown. Here, we studied genome-wide gene expression using transcriptome analysis (RNA-seq) and global levels of DNA (hydroxy)methylation (5(h)mC) using high-performance liquid chromatography-tandem mass spectrometry in 5-HTT wild-type (5-HTT^+/+) and 5-HTT homozygous knockout (5-HTT^−/−) rats across life (postnatal day [PND] 8, 14, 21, 35, and 70) in the medial prefrontal cortex (mPFC); a brain region with an extensive serotonergic innervation involved in several neuropsychiatric endophenotypes. We observed most gene expression changes in the mPFC during early postnatal life (PND8) and found at this time point an enrichment of genes linked to neuronal and developmental processes like neurotransmission, neuropeptide signaling, and cell migration. Genome-wide DNA 5(h)mC analysis showed a global increase in 5-hydroxymethylcytosine (5hmC) in the mPFC during development in both genotypes and a significant increase in global 5hmC in 5-HTT^−/− compared to 5-HTT^+/+ rats at PND35. The differences in the regulation of gene expression in 5-HTT^−/− versus 5-HTT^+/+ rats during early postnatal life can dysregulate neurodevelopmental processes resulting in aberrant brain wiring and functioning. This can result in lifelong consequences for prefrontal context-dependent executive functioning.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.22973","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244465","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":"Islet-2 Is Required for the Survival of Islet-Expressing Retinal Ganglion Cells but Not for Their Pathfinding to the Contralateral Dorsal Lateral Geniculate Nucleus","authors":"Sadaf Abed,&nbsp;David A. Feldheim","doi":"10.1002/dneu.22978","DOIUrl":"https://doi.org/10.1002/dneu.22978","url":null,"abstract":"<div>\u0000 \u0000 <p>Retinal ganglion cells (RGCs) exhibit remarkable diversity owing to their expression of developmentally expressed transcription factors. Many transcription factors are expressed in unique RGC populations, but their roles within these populations remain undiscovered. The transcription factor Islet-2 (<i>Isl2</i>) is expressed in approximately 30%–40% of contralateral projecting RGCs. Previous work by others found increased ipsilateral innervation of the dorsal lateral geniculate nucleus (dLGN) in <i>Isl2</i> mutant mice, implicating <i>Isl2</i> in promoting a contralateral RGC axon trajectory. Since <i>Isl2</i> mutant mice suffer early neonatal lethality, the role of <i>Isl2</i> in RGC specification has not been fully explored. To test the role of <i>Isl2</i> in RGC development, two lines of retina-specific <i>Isl2</i> mutant mice were generated. Contrary to the findings in <i>Isl2</i> null mice, <i>Isl2</i> retinal deletion does not lead to early postnatal lethality or increased ipsilateral projections to the dLGN. Instead, there is a significant reduction in the size of the dLGN and a mild reduction in the size of the ipsilateral projection to the dLGN. Retinal <i>Isl2</i> mutants also exhibit diminished expression of genes characteristic of <i>Isl2</i>-expressing RGCs, along with increased retinal cell death during development. These findings suggest that <i>Isl2</i> is required for the development and survival of <i>Isl2</i>-expressing RGC subtypes.</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":"144220140","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":"Disruption of Embryogenesis Biomarkers: A Critical Issue for Autism Therapeutics","authors":"Abdulla A. Al-dulaimi,&nbsp;Turakulov Rustam,&nbsp;Mahmood Jawad,&nbsp;Nina N. Kanshina,&nbsp;Lalji Baldaniya,&nbsp;Bhanu Juneja,&nbsp;Kamlesh Chaudhary,&nbsp;Swati Sharma,&nbsp;Subasini Uthirapathy,&nbsp;Zainab Ahmed Abass","doi":"10.1002/dneu.22976","DOIUrl":"https://doi.org/10.1002/dneu.22976","url":null,"abstract":"<div>\u0000 \u0000 <p>Recent advancements in the field of autism research have led to significant progress in identifying biomarkers associated with autism spectrum disorder (ASD). This article provides a comprehensive update on the current landscape of biomarkers, encompassing genetic, neurobiological, and behavioral indicators. Genetic studies have identified numerous candidate genes and chromosomal abnormalities linked to ASD, highlighting the heritable nature of the disorder. Neuroimaging techniques, including functional magnetic resonance imaging (MRI) and diffusion tensor imaging, have revealed distinct patterns of brain connectivity and structural anomalies that correlate with ASD symptoms. Additionally, electrophysiological measures, such as event-related potentials and electroencephalography, offer insights into the neural mechanisms underlying social cognition and sensory processing in individuals with autism. Emerging research on metabolic and inflammatory biomarkers also shows promise in elucidating the biological pathways involved in ASD. Although these findings provide valuable avenues for early diagnosis and personalized treatment strategies, challenges remain in translating biomarker research into clinical practice. This review emphasizes the need for continued exploration of biomarkers to enhance our understanding of ASD and improve diagnostic accuracy and intervention efficacy for affected individuals.</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":"144220138","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":"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}