Developmental Neurobiology最新文献

{"title":"A Novel Homozygous TBC1D2B Variant Disrupts Functional Domains and Suggests Impaired Rab-GTPase Regulation in Neurodevelopmental Disorder","authors":"Murat Ozturk,&nbsp;Cahide Bulut Arslan,&nbsp;Ekrem Akbulut,&nbsp;Esra Habiloglu,&nbsp;Esra Yaylı,&nbsp;Zehra Oya Uyguner","doi":"10.1002/dneu.22998","DOIUrl":"https://doi.org/10.1002/dneu.22998","url":null,"abstract":"<div>\u0000 \u0000 <p>Recent reports have linked biallelic loss-of-function variants in the <i>TBC1D2B</i> gene to neurodevelopmental disorder with seizures and gingival overgrowth (NEDSGO) (OMIM 619323), a rare condition characterized by seizures and gingival hyperplasia. However, due to the limited number of reported cases, the phenotypic diversity of this syndrome remains poorly characterized. This study reports four affected children from a consanguineous family in Türkiye, in whom a novel variant in this gene was identified. All individuals underwent clinical examination, electroencephalography (EEG), brain magnetic resonance imaging (MRI), histopathological evaluation, and genetic analyses. A novel homozygous truncating variant in the <i>TBC1D2B</i> gene was identified. In silico protein structure modeling was performed to investigate the potential impact of the variant. The identified c.323_324delinsAA; p.(Phe108Ter) variant causes premature protein truncation, resulting in the loss of key functional domains, such as Rab-GAP-TBC, coiled-coil, and PH (pleckstrin homology). All patients exhibited developmental delay (DD), epileptic seizures, gingival fibromatosis, and craniofacial anomalies. The growth delay seen in both of our patients, also described in an earlier case with the same gene variant, suggests that this may be a clinical feature of the syndrome. Binding pocket analysis revealed marked reductions in putative protein interaction regions, suggesting a loss-of-function effect due to the mutation. These findings reveal previously unrecognized aspects of both the genetic and clinical spectrum of NEDSGO syndrome caused by variants in the <i>TBC1D2B</i> gene. The resulting data underscore that disruption of structural protein regions directly contributes to the phenotype of this rare disorder.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 4","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929689","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":"Hepatic Encephalopathy: Insights Into the Impact of Metabolic Precipitates","authors":"Udit Kumar Dash,&nbsp;Aparna Tripathi,&nbsp;Debashree Mazumdar,&nbsp;Dusmanta Podh,&nbsp;Santosh Singh","doi":"10.1002/dneu.22999","DOIUrl":"https://doi.org/10.1002/dneu.22999","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatic failure is a severe condition marked by the progressive or sudden loss of liver function, broadly categorized into acute liver failure (ALF), which develops within days to weeks, and chronic liver failure (CLF), which evolves over months or years. Both forms can lead to serious complications such as jaundice, impaired detoxification, portal hypertension, ascites, multi-organ dysfunction, and coagulation disorders. A significant neuropsychiatric consequence of liver failure is hepatic encephalopathy (HE), a spectrum of cognitive, motor, and behavioral abnormalities. Although elevated ammonia levels have long been implicated as a central factor in the pathogenesis of HE, emerging evidence suggests that other metabolic toxins also play critical roles. These include manganese (Mn), altered glucose metabolism, short-chain fatty acids (SCFAs), mercaptans, and gamma-aminobutyric acid (GABA). This review aims to explore the multifactorial metabolic landscape contributing to HE, highlighting the potential synergistic effects and mechanistic roles of these blood-borne precipitates. Understanding these diverse metabolic contributors may pave the way for more comprehensive diagnostic and therapeutic approaches beyond the traditional focus on ammonia.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 4","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929684","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":"Neurodevelopmental Outcomes of Mycotoxins Exposure and Effect on Brain Development in Infants and Young Children","authors":"Laure Viviane Ndam Ngoungoure,&nbsp;Wilfred Angie Abia,&nbsp;Brice Vincent Ayissi Owona,&nbsp;Yacouba Foupouapouognigni,&nbsp;Ferdinand Kouoh Elombo,&nbsp;Herman Philipe Njitoyap Nfombouot,&nbsp;Epole Ngolle Ntungwe,&nbsp;Frederic N. Njayou,&nbsp;Angéle N. Tchana,&nbsp;Paul F. Moundipa","doi":"10.1002/dneu.23000","DOIUrl":"https://doi.org/10.1002/dneu.23000","url":null,"abstract":"<div>\u0000 \u0000 <p>This comprehensive literature review was conducted to identify relevant studies on mycotoxins and brain development in children. Existing studies suggest that mycotoxin exposure during critical periods of brain development may lead to neurocognitive impairments in children. Some studies have reported associations between mycotoxin exposure and reduced cognitive abilities, impaired motor skills, and behavioral problems. Additionally, mycotoxins have been shown to disrupt neural signaling pathways and interfere with neurotransmitter function, potentially contributing to neurodevelopmental disorders. This comprehensive review has provided a comprehensive overview of the possible evidence on the association between mycotoxin exposure and brain development in children and identified areas for future research.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 4","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929690","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":"Neuroinflammatory Pathways in Autism Spectrum Disorder: Unraveling the Role of Sirtuin 1 in Clinical Samples","authors":"Merve Cikili-Uytun,&nbsp;Esra Yurumez,&nbsp;Banu Kaymak,&nbsp;Ozlem Dogan,&nbsp;Humeyra Hilal Ozturk,&nbsp;Beyza Nur Baysar Kanoglu,&nbsp;Didem Behice Oztop","doi":"10.1002/dneu.22981","DOIUrl":"https://doi.org/10.1002/dneu.22981","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Despite extensive research, the etiological factors contributing to autism spectrum disorder (ASD) remain incompletely understood, with potential influences ranging from genetic predispositions to environmental factors. Sirtuin 1 (SIRT1), an NAD⁺-dependent histone deacetylase involved in mitigating oxidative stress and its association with other neurodevelopmental disorders, explores its function in ASD. This study aimed to elucidate the relationship between SIRT1 and inflammatory cytokines, specifically interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), in patients with ASD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <p>This study enrolled 46 children diagnosed with ASD and 44 typically developing (TD) children aged 36–120 months. Diagnosis of ASD was confirmed using DSM-5 criteria through clinical and observational assessments conducted by three experienced child and adolescent psychiatrists at the outpatient Infant Mental Health unit of Ankara University. The Childhood Autism Rating Scale (CARS) and the Repetitive Behavior Scale-Revised (RBS-R) were used to assess autistic behaviors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <p>Analysis of serum levels of SIRT1, IL-6, and TNF-α revealed no significant differences between the ASD group and the TD group. Correlation analysis demonstrated a significant positive relationship between SIRT1 levels and IL-6 (<i>r</i> = 0.71, <i>p</i> &lt; 0.001) and TNF-α (<i>r</i> = 0.86, <i>p</i> &lt; 0.001). Additionally, regression phenomena exhibited a moderate negative correlation with IL-6 (<i>r</i> = −0.32, <i>p</i> = 0.02) and TNF-α (<i>r</i> = −0.38, <i>p</i> = 0.008). Age was positively correlated with levels of IL-6, TNF-α, and SIRT1. However, no correlations were found between these parameters and gender.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <p>These findings do not support the hypothesized role of disturbances in the expression of circulating cytokines and SIRT1 as indicators of systemic inflammation in autism. Further longitudinal studies should examine these immune markers in blood samples from large sample sizes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 4","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144918842","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":"Dectin-1 Drives Diabetic Retinopathy via Inducing Microglia-Mediated Inflammation and Blood–Retinal Barrier Breakdown","authors":"Lei Zhang,&nbsp;Sumei Zhang,&nbsp;Yingjun Li,&nbsp;Zhen Yang,&nbsp;Weikang Hu,&nbsp;Hongmei Bai,&nbsp;Wenjing Zhou,&nbsp;Zihan Wang,&nbsp;Mingcong Li,&nbsp;Shengquan Zhang,&nbsp;Rongfeng Liao","doi":"10.1002/dneu.22997","DOIUrl":"https://doi.org/10.1002/dneu.22997","url":null,"abstract":"<div>\u0000 \u0000 <p>Diabetic retinopathy (DR), a prevailing manifestation among diabetic patients, occurs as a major sight-threatening disorder. <i>Dectin-1</i>, as an innate immune receptor, has been notified as a critical modulator of diabetes mellitus. In this context, the implication of <i>Dectin-1</i> in the process of DR that is still a conundrum will be addressed here. The diabetic mouse model was established by intraperitoneal injection of streptozotocin (STZ), and human microglia cells (HMC3) were subjected to high glucose (HG) to create cellular models of diabetes. Glucose level and body weight were recorded in mice. Reverse transcription-quantitative PCR (RT-qPCR) and western blotting checked <i>Dectin-1</i> expression. RT-qPCR, enzyme-linked immunosorbent assay (ELISA), and western blotting appraised the inflammatory levels. Immunofluorescence staining and western blotting ascertained the expression of IBA-1 and tight junction proteins. Besides, western blotting also examined albumin expression. Terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay and western blotting assayed the apoptotic level. <i>Dectin-1</i> was highly expressed in both retinal tissues of diabetic mice and HG-exposed HMC3 cells. <i>Dectin-1</i> antagonist laminarin (LAM) observably repressed microglia activation, inflammatory reaction, and blood–retinal barrier (BRB) leakage both in vitro and in vivo. Moreover, LAM produced anti-apoptotic effect in vivo. To sum up, <i>Dectin-1</i> inhibitor might block the inflammatory cascade and protect against BRB disruption in DR.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 4","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144814907","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":"Spinal Astrocytes in Chronic Visceral Pain","authors":"Wenfeng Li,&nbsp;Lili Zhang,&nbsp;Shaozong Chen","doi":"10.1002/dneu.22996","DOIUrl":"https://doi.org/10.1002/dneu.22996","url":null,"abstract":"<div>\u0000 \u0000 <p>Chronic visceral pain is the primary symptom of functional gastrointestinal disorders, affecting up to 20% of the population. It involves peripheral sensitization in the peripheral nervous system and central sensitization in the central nervous system (CNS). In recent years, related research has extended from neurons to glial cells, particularly astrocytes in the spinal cord, which become activated, exhibit enhanced coupling, and show higher sensitivity to pain mediators. This review discusses the mechanisms of spinal astrocytes in different animal models of visceral pain. A role of spinal astrocytes in the pathogenesis of visceral pain is also emerging, and astrocytes are likely to be a target for the future therapies of chronic visceral pain.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 4","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144814684","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":"Neonatal Procedural Pain Disrupts Phosphorylation of KCC2 in the Spinal Cord","authors":"Mathilde Baudat,&nbsp;Elbert A. J Joosten,&nbsp;Sinno H. P. Simons,&nbsp;Daniël L. A. van den Hove,&nbsp;Renzo J. M. Riemens","doi":"10.1002/dneu.22993","DOIUrl":"https://doi.org/10.1002/dneu.22993","url":null,"abstract":"<p>Neonatal procedural pain experienced in the neonatal intensive care unit can lead to long-lasting remodeling of the central nervous system and, in particular, of the spinal nociceptive network. Preclinical studies indicate a disrupted inhibitory versus excitatory balance in the spinal cord due to reduced γ-aminobutyric acid (GABA) ergic neurotransmission. During neonatal development a GABAergic shift occurs, which is regulated by the potassium-chloride co-transporter 2 (KCC2) and its oxytocin receptor (OXTR)-dependent phosphorylation at the serine 940 residue (pKCC2). As DNA methylation of <i>Oxtr</i> is sensitive to early life adversity, such as neonatal procedural pain, we hypothesized that neonatal procedural pain reduces <i>Oxtr</i> methylation in the lumbar spinal cord and subsequently prevents the developmental increase in KCC2 and pKCC2. Using a rat model of repetitive neonatal procedural pain, four needle pricks were applied to the left hind paw every day from postnatal day (P)0 to P7. Spinal cord samples were collected at P0 and P10 to assess the levels of KCC2 and pKCC2 via Western blot analysis. Additionally, spinal <i>Oxtr</i> methylation was quantified using bisulfite pyrosequencing. The results indicated that neonatal procedural pain downregulates spinal pKCC2 levels, while KCC2 levels remain unchanged. These findings suggest a disrupted KCC2-dependent chloride outflow and support the hypothesis that neonatal procedural pain disrupts the GABAergic shift. A developmental decrease in pKCC2/KCC2 levels was also observed in the ipsilateral spinal cord of P10 animals, indicating the involvement of other post-translational mechanisms in the developmental regulation of spinal KCC2. Methylation of the <i>Oxtr</i> does not seem to be related to the disturbed GABAergic shift, given that no significant changes in <i>Oxtr</i> promoter methylation were detected. Overall, this study demonstrates that neonatal procedural pain disrupts spinal KCC2 phosphorylation and supports the hypothesis that neonatal procedural pain alters the GABAergic shift in the spinal cord.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 4","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.22993","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144814685","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":"Could the Polymorphisms of DOCK4 (rs147636134), SYNGAP1 (rs199759879), and FOXP1 (rs767001715) be the Primary Risk Factors for Bipolar Disorder and Autism Spectrum Disorder?","authors":"Elvan Çiftçi,&nbsp;Nimet Sağlam,&nbsp;Tayfun Gözler,&nbsp;İpek Yüksel,&nbsp;Neriman Kilit,&nbsp;İlknur Bozkurt,&nbsp;Muhsin Konuk,&nbsp;Korkut Ulucan,&nbsp;Nevzat Tarhan","doi":"10.1002/dneu.22995","DOIUrl":"https://doi.org/10.1002/dneu.22995","url":null,"abstract":"<p>Autism spectrum disorder (ASD) and bipolar disorder (BD) are psychiatric diseases that may overlap in common neurodevelopmental and genetic basis. Forkhead Box P1 (FOXP1), Synaptic Ras GTPase-activating protein 1 (SYNGAP1), and Dedicator of Cytokinesis 4 (DOCK4) genes are critical for synaptic plasticity, neuronal communication, and brain development. This study aims to investigate the association of <i>FOXP1</i> (rs767001715), <i>SYNGAP1</i> (rs199759879), and <i>DOCK4</i> (rs147636134) polymorphisms with ASD and BD and to determine the effects of genetic variations on disease pathogenesis in the Turkish population. This study was conducted with a total of 200 participants, including 50 ASD patients, 50 BD patients, and 100 healthy controls. DNA was isolated from peripheral blood samples, and <i>FOXP1</i>, <i>SYNGAP1</i>, and <i>DOCK4</i> polymorphisms were genotyped using real-time PCR. The distribution of genetic variants was compared between patient groups and healthy controls. The chi-square test was applied for statistical analyses. In terms of <i>FOXP1</i> (rs767001715), <i>SYNGAP1</i> (rs199759879), and <i>DOCK4</i> (rs147636134) polymorphisms examined in the study, no statistically significant difference was found between the ASD and BD patient groups and the healthy control group (<i>p</i> &gt; 0.05) in the Turkish population. In addition, it was determined that these variants had allele frequencies compatible with global population data. However, due to the limited sample size, these results cannot be generalized. Further large-scale population analyses and functional studies are needed to investigate the association of these genes with ASD and BD in more detail.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 4","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.22995","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144814683","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":"Efficacy of midazolam in the Treatment of Acute Convulsions in Children and Its Effects on Convulsive Brain Tissue Injury","authors":"Jing Zhang,&nbsp;Jing Dong,&nbsp;Ling Jiang,&nbsp;Lin Ge,&nbsp;Ran Dong","doi":"10.1002/dneu.22992","DOIUrl":"https://doi.org/10.1002/dneu.22992","url":null,"abstract":"<div>\u0000 \u0000 <p>This study focused on addressing the efficacy of midazolam in the treatment of acute convulsions in children and its effects on convulsive brain tissue injury.</p>\u0000 <p>A total of 124 children with acute convulsions were separated into the control group and the observation group according to the random number table method. Children in the control group received intravenous injection therapy with diazepam (0.3–0.5 mg/kg); those in the observation group received midazolam buccal mucosa administration treatment (different doses for different age groups). The total effective rate of treatment and adverse reactions were observed. The number of children whose convulsions were controlled within 1, 3, and 5 minutes after medication, the time to initial convulsion control, the number of children who experienced recurrence within 10 minutes after control, and the time to recurrence control were recorded. Juvenile (21-day-old) Sprague-Dawley rats were separated into blank control, model, low-dose midazolam, medium-dose midazolam, and high-dose midazolam groups. Rats in the midazolam groups were injected intraperitoneally with different doses of midazolam. The convulsive model rats were prepared by intraperitoneal injection of pentylenetetrazol, and the emergence time and duration time of convulsions were recorded. The convulsion grade of rats was evaluated. The rats were euthanized, and their brain tissues were taken. The pathological morphological changes in the brain tissues were observed, and glial fibrillary acidic protein (GFAP) and gamma-aminobutyric acid (GABA) expression levels in the brain tissues were tested.</p>\u0000 <p>The observation group demonstrated a higher total effective treatment rate, a greater number of children whose convulsions were controlled within 3 and 5 minutes of treatment, a shorter average time to convulsion control, a lower recurrence rate within 10 minutes after initial control, a shorter time to control recurrent convulsions, and a lower incidence of adverse reactions compared to the control group. Convulsive model rats that received medium- and high-dose midazolam displayed prolonged emergence time of convulsions, shorter duration, and lower convulsion grade. In convulsive model rats, the nucleus of hippocampal neurons was deeply stained and showed pyknosis; the arrangement of neurons was disordered; the cells were loose and edematous. In the convulsive model, rats received medium- and high-dose midazolam, and the neuron pyknosis and cell oedema were alleviated. In the hippocampus of convulsive model, rats received high-dose midazolam, GFAP expression levels were reduced, and GABA expression levels were raised (<i>p</i> &lt; 0.05).</p>\u0000 <p>For children with acute convulsions, midazolam buccal mucosa administration can rapidly control convulsive seizures and reduce recurrence rates with high safety. High-dose midazolam can ameliorate brain tissue injury in convulsed rats, redu","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 4","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144767859","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":"EMC10 Gene Variants May Cause Dual Molecular Effects on the Neuropsychiatric Disease Pattern","authors":"Hilmi Bolat,&nbsp;Dilan Genç Akdağ,&nbsp;Gül Ünsel-Bolat","doi":"10.1002/dneu.22994","DOIUrl":"https://doi.org/10.1002/dneu.22994","url":null,"abstract":"<div>\u0000 \u0000 <p>The <i>EMC10</i> gene on chromosome 19 encodes one of the highly conserved endoplasmic reticulum membrane complexes (EMC). Specific mutations in <i>EMC10</i> cause a disorder known as neurodevelopmental disorder with dysmorphic facies and variable seizures (NEDDFAS) (OMIM #619264), characterized by global developmental delay and dysmorphic facial features, which become apparent in early childhood. This study aims to present the clinical data associated with a novel variant of a patient diagnosed with NEDDFAS (OMIM #619264), a condition rarely reported in the literature. By examining the phenotypic implications and molecular mechanisms of pathogenic variants in the <i>EMC10</i> gene, this study seeks to contribute to a better understanding of the genetic and clinical spectrum of the disease. Our case was followed up in the Child and Adolescent Psychiatry clinic with the diagnosis of intellectual disability. Initial genetic testing included karyotype analysis, <i>FMR1</i> CGG repeat analysis, and chromosomal microarray analysis. Subsequently, whole-exome sequencing (WES) was performed, and Sanger sequencing was used to confirm the identified variant and conduct familial segregation analysis. We identified a novel homozygous frameshift variant in the <i>EMC10</i> gene, NM_206538.4:c.431del, resulting in NP_996261.1:p.Asp144AlafsTer3 using WES. This variant was classified as pathogenic (P) according to ACMG criteria, which was clinically relevant to the patient's condition. Segregation analysis revealed that both the mother and the father were heterozygous carriers of this variant. To date, the phenotype associated with this variant has been reported in 31 individuals from 16 different families. To our knowledge, our case is the first reported patient in the Turkish population carrying an <i>EMC10</i> gene variant. Among reported cases, variations in symptom distribution and severity have been observed. We propose that <i>EMC10</i> gene variants may exhibit dual molecular effects. There are two types of neurodevelopmental clinical presentations: (1) a classic disease pattern with mild-to-moderate intellectual disability (ID) and no neurological findings and (2) a progressive disease pattern with severe ID, hypotonia, and abnormalities in gait.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 4","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740520","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}