Journal of neurogenetics最新文献

{"title":"Congenital mirror movements in a family: Outcomes associated with DCC mutations.","authors":"Arife Derda Yücel Şen, Kursat Bora Carman, Çağrı Doğan, Mustafa Şen, Coşkun Yarar","doi":"10.1080/01677063.2025.2525868","DOIUrl":"10.1080/01677063.2025.2525868","url":null,"abstract":"<p><strong>Introduction: </strong>Congenital mirror movement disorder refers to involuntary movements on one side of the body that mimic the deliberate movements on the opposite side. Congenital mirror movement is primarily associated with mutations in the DCC netrin-1 receptor (DCC) gene.</p><p><strong>Case presentation: </strong>A 3-year-old child had been involuntarily grasping with one hand and then the other from infancy. His neuromotor development corresponded with that of his contemporaries. Identical unusual movements were also observed in his father, uncle, and grandmother within his family heritage. In the family where identical observations were noted throughout three generations, the mildest manifestations were reported in the grandmother, but our patient, the index case, had more significant symptoms. The quadruple WES study of the family indicated that all clinically symptomatic individuals harbored a nonsense mutation in the DCC gene.</p><p><strong>Conclusions: </strong>Mirror movements, typically identified in childhood, may result from genetic or neurological disorders. This study presents four individuals from the same family diagnosed with congenital mirror movement disorder.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":" ","pages":"65-69"},"PeriodicalIF":2.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575686","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":"Impact of gene-gene interactions in Progressive Supranuclear Palsy: new genetic perspectives in the Asian-Indian population.","authors":"Saikat Dey, Monojit Debnath, Ramchandra Yelamanchi, Nitish Kamble, Vikram V Holla, Rohan R Mahale, Pramod Kumar Pal, Ravi Yadav","doi":"10.1080/01677063.2025.2500953","DOIUrl":"10.1080/01677063.2025.2500953","url":null,"abstract":"<p><p>Genes play an important role in the risk of Progressive Supranuclear Palsy (PSP). Some of the major risk genes identified for PSP include <i>MAPT</i>, <i>STX6</i>, <i>MOBP</i>, and <i>EIF2AK3</i> in several ethnic groups. However, the interactions among these genes have not been explored in PSP. Therefore, this prospective case-control study aimed to explore the impact of gene-gene interactions in patients with PSP (n = 106) and healthy subjects (n = 109) of Indian ethnicity. Eight single nucleotide polymorphisms (SNPs) of <i>MAPT</i> gene (rs1467967, rs242557, rs3785883, rs2471738, rs8070723, rs7521, rs12185268, and rs62063857, and two SNPs of <i>STX6</i> gene (rs3747957 and rs1411478), one SNP each from <i>MOBP</i> (rs1768208) and <i>EIF2AK3</i> (rs7571971) genes were genotyped by TaqMan Alleleic Discrimination Assay in all the study participants. Gene-gene interactions among these 12 SNPs were performed using the multi-dimensionality reduction (MDR) test. The combination of SNPs from the <i>MAPT</i> gene (rs1467967, rs242557, rs3785883), along with <i>STX6</i> (rs1411478) and <i>MOBP</i> (rs1768208), appeared to be the best five-locus model (<i>p</i> < 0.001), suggesting strong interactions among <i>MAPT</i>, <i>STX6</i> and <i>MOBP</i> genes in modulating the risk of PSP. Strong synergistic interactions were observed within <i>MAPT</i> gene (rs1467967, rs244557, rs3785883, rs7521, and rs2471738), and between <i>MAPT</i> (rs7521) and <i>MOBP</i> (rs1768208). Additionally, moderately strong synergistic interactions were found between (i) <i>MOBP</i> (rs1768208) and <i>STX6</i> (rs1411478), and (ii) <i>MOBP</i> (rs1768208) and <i>MAPT</i> (rs3785883) genes. The findings of this study suggest significant impact of gene-gene interactions amongst <i>MAPT</i>, <i>STX6</i>, and <i>MOBP</i> genes in modulating the risk of PSP. This implies that epistatic interactions might constitute an important mechanism in delineating the genetic basis of PSP.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":" ","pages":"70-76"},"PeriodicalIF":2.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078621","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 ataxin-2 protein is required in kenyon cells for RNP-granule assembly and appetitive long-term memory formation.","authors":"Camilla Roselli, Jens Hillebrand, Jenifer Kaldun, Vernon Leander Monteiro, Thomas Hurd, Simon G Sprecher, Tamara Boto, Mani Ramaswami","doi":"10.1080/01677063.2025.2537054","DOIUrl":"10.1080/01677063.2025.2537054","url":null,"abstract":"<p><p>Ribonucleoprotein granules (mRNP granules) are thought to contribute to the control of neuronal mRNA translation required for consolidation of long-term memories. Consistent with this, the function of Ataxin-2 in mRNA granule assembly has been shown to be required for long-term olfactory habituation (LTH) in <i>Drosophila</i>, a form of non-associative memory. Knockdown of Ataxin-2 in either local interneurons (LNs) or projection neurons (PNs) of the insect antennal lobe disrupts LTH while leaving short-term habituation intact, leading to a model in which Ataxin-dependent translational control is required in both presynaptic and postsynaptic elements of the LN-PN synapse, whose potentiation has been causally linked to LTH. Here we use novel and established methods for cell-type specific perturbation to ask: (a) whether Ataxin-2 controls mRNA granule assembly in cell types beyond the few that have been examined; and (b) whether it functions not only in LTH, but also for long-term olfactory associative memory (LTM). We show that Ataxin-2 controls mRNP granule assembly in additional neuronal types, namely Kenyon Cells (KCs) that encode associative memory, as well as more broadly in non-neuronal cells, e.g. in nurse cells in the egg chamber. Furthermore, selective knockdown of Atx2 in α/β and α'/β' KCs blocks appetitive long-term but not short-term associative memories. Taken together these observations support a hypothesis that Ataxin-2 dependent translational control is widely required across different mnemonic circuits for consolidation of respective forms of long-term memories.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":" ","pages":"54-64"},"PeriodicalIF":2.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775590","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":"A novel role of Arp2/3 complex in the forgetting behavior of <i>Caenorhabditis elegans</i> to <i>Pseudomonas aeruginosa</i> PA14.","authors":"Xin Zhao, Xinyu Li, Hua Bai, Xiaoying Liu, Yaqi Deng, Yu Duan, Qi Wang, Wei Zou","doi":"10.1080/01677063.2025.2494523","DOIUrl":"10.1080/01677063.2025.2494523","url":null,"abstract":"<p><p>Forgetting behavior is a common phenomenon that has been widely studied in various model organisms, including <i>Caenorhabditis elegans</i> (<i>C. elegans</i>), Drosophila, and mammals such as mice and humans. Understanding the mechanisms underlying forgetting can provide valuable insights into potential treatments for memory-related disorders. In this study, <i>C. elegans</i> was used as a model organism to establish a forgetting model based on the PA14 pathogen. A proteomic analysis of signaling pathways involved in forgetting revealed the role of the Arp2/3 complex in regulating pathogen-induced forgetting. Manipulation of genes encoding the components of the Arp2/3 complex (<i>arx-1</i>, <i>arx-2</i>, <i>arx-3</i>, <i>arx-5</i>, and <i>arx-7</i>) led to a reduction in the duration of pathogen-induced forgetting. Additionally, one hour after pathogen removal, a significant decrease in the mRNA levels of <i>arx-5</i> and <i>arx-7</i> was observed, along with a reduction in <i>arx-2::mCherry</i> fluorescence in specific tissues of <i>C. elegans</i>. This study demonstrates that <i>C. elegans</i> exhibits forgetting behavior towards PA14, with a forgetting duration of approximately 2 hours. Pathogen-induced forgetting is associated with an increase in heterogeneous proteins localized to the cytoskeleton. Moreover, the expression levels of genes related to the Arp2/3 complex (<i>arx-1</i>, <i>arx-2</i>, <i>arx-3</i>, <i>arx-5</i>, and <i>arx-7</i>) are reduced, inhibiting cytoskeleton nucleation in cells. This inhibition may contribute to the observed pathogen-induced forgetting in <i>C. elegans</i> in response to PA14.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":" ","pages":"39-53"},"PeriodicalIF":2.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012386","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":"Venerose: a nuptial gift with implications.","authors":"Deepanshu N D Singh, Matthias Soller","doi":"10.1080/01677063.2025.2473095","DOIUrl":"10.1080/01677063.2025.2473095","url":null,"abstract":"<p><p>Males transfer many components in seminal fluid along with sperm during mating. While sex peptide is well established as a key regulator of female reproductive behaviour and success, the roles of other seminal fluid components remain less understood. A new <i>Drosophila</i> study now reveals functions for a sexually transmitted sugar in providing nutritional value and acting on nutrient-sensing neurons in the brain to maximize reproductive success. Here, we highlight the key findings of this study and explore the potential role of this sugar in male quality assessment by females and in modulation of cryptic female choice.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":" ","pages":"1-3"},"PeriodicalIF":1.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11996059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567412","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":"The novel T107I Inherited prion disease can present as a clinical and biomarker mimic of familial Alzheimer's disease.","authors":"Leah Holm-Mercer, Thomas Coysh, Tze How Mok, Peter Rudge, Zita Reisz, Claire Troakes, Safa Al-Sarraj, Tracy Campbell, Laszlo L P Hosszu, Jan Bieschke, Fuquan Zhang, Jonathan D F Wadsworth, Colin Smith, Jenna Jenkinson, Timothy Rittman, Sebastian Brandner, Zane Jaunmuktane, John Collinge, Simon Mead","doi":"10.1080/01677063.2024.2440395","DOIUrl":"10.1080/01677063.2024.2440395","url":null,"abstract":"<p><p>Inherited prion diseases (IPD) secondary to mutations of the prion protein gene, <i>PRNP,</i> exhibit diverse clinical phenotypes, capable of mimicking numerous primary neurodegenerative conditions. We describe the clinical phenotype and neuropathological findings in a family from County Limerick in Ireland presenting with Alzheimer's disease-like cognitive decline and motor symptoms caused by a novel missense mutation of <i>PRNP.</i> This mutation occurs in the <i>PRNP</i> central lysine cluster (CLC; codon 101-110), resulting in substitution of threonine with isoleucine at codon 107 (T107I). This case series highlights that IPD can be hard to distinguish from overlapping clinical syndromes seen in other neurodegenerative diseases. We also discuss similarities and differences of the novel mutation T107I to other pathogenic mutations of the CLC of <i>PRNP</i>.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":" ","pages":"16-22"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950278","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":"<i>Drosophila WDFY3</i>/<i>Bchs</i> overexpression impairs neural function.","authors":"Marek B Körner, Akhil Velluva, Linnaeus Bundalian, Knut Krohn, Kathleen Schön, Isabell Schumann, Jessica Kromp, Andreas S Thum, Antje Garten, Julia Hentschel, Rami Abou Jamra, Achmed Mrestani, Nicole Scholz, Tobias Langenhan, Diana Le Duc","doi":"10.1080/01677063.2025.2465536","DOIUrl":"10.1080/01677063.2025.2465536","url":null,"abstract":"<p><p>Pathogenic variants in <i>WDFY3</i>, a gene encoding for an autophagy adaptor termed ALFY, are linked to neurodevelopmental delay and altered brain size in human probands. While the role of <i>WDFY3</i> loss-of-function is extensively studied in neurons, little is known about the effects of <i>WDFY3</i> upregulation in different cell types of the central nervous system (CNS). We show that overexpression of the <i>Drosophila melanogaster WDFY3</i> ortholog, <i>Bchs</i>, in either glia or neurons impaired autophagy and locomotion. <i>Bchs</i> glial overexpression also increased VNC size and glial nuclei number significantly, whereas neuronal <i>Bchs</i> overexpression affected wing and thorax morphology. We identified 79 genes that were differentially expressed and overlapped in flies that overexpress <i>Bchs</i> in glial and neuronal cells, respectively. Additionally, upon neuronal <i>Bchs</i> overexpression differentially expressed genes clustered in gene ontology categories associated with autophagy and mitochondrial function. Our data indicate that glial as well as neuronal <i>Bchs</i> upregulation can have detrimental outcomes on neural function.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":" ","pages":"23-38"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502064","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":"Vitamin D receptor FokI polymorphism as a risk factor for painful diabetic neuropathy in type 2 diabetes mellitus patients.","authors":"Aurelia Vania, Dewa Putu Gde Purwa Samatra, I Made Oka Adnyana, Made Ratna Saraswati, Agus Eka Darwinata, I Putu Eka Widyadharma","doi":"10.1080/01677063.2025.2473705","DOIUrl":"10.1080/01677063.2025.2473705","url":null,"abstract":"<p><p>Painful diabetic neuropathy (PDN) is a common complication in patients with type 2 diabetes mellitus (T2DM) with disruption of vitamin D (VD) activity as one of the risk factors. Active VD exerts its biological functions through the vitamin D receptor (VDR), which polymorphisms in the VDR gene can impair. This study aims to establish VDR FokI and ApaI polymorphisms as risk factors for PDN. This case-control study used samples from T2DM patients with and without PDN. Neuropathic pain was diagnosed using the DN4 questionnaire, while FokI and ApaI polymorphisms were examined using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method. Other factors examined included gender, hypertension, current insulin use, obesity, HbA1c levels, and dyslipidemia. A total of 64 subjects were involved in the study. The FokI polymorphism (CT+TT genotype) was a significant risk factor for PDN (OR 4.20; 95% CI [1.47-11.94]; <i>p</i> = 0.012). The T allele in the FokI polymorphism significantly increased the risk of PDN by 2.8 times (OR 2.78; 95% CI [1.28-6.01], <i>p</i> = 0.014). The ApaI polymorphism was not significantly associated with PDN. Diabetes duration ≥4.5 years and uncontrolled diabetes were other significant risk factors for PDN. Multivariate analysis identified three significant variables: FokI polymorphism (OR 5.00; 95% CI [1.37-18.24], <i>p</i> = 0.015), insulin use (OR 4.95; 95% CI [1.37-17.87], <i>p</i> = 0.015), and uncontrolled diabetes (OR 3.47; 95% CI [1.03-11.69], <i>p</i> = 0.045). The VDR FokI polymorphism with the T allele is a significant genetic risk factor for PDN in T2DM patients. The VDR ApaI polymorphism was not a significant risk factor for PDN.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":" ","pages":"7-15"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605212","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":"Two tales of therapeutic innovations for Leigh syndrome spectrum.","authors":"Wei-Sheng Lin","doi":"10.1080/01677063.2025.2473087","DOIUrl":"10.1080/01677063.2025.2473087","url":null,"abstract":"<p><p>Leigh syndrome spectrum is the most common form of childhood-onset mitochondrial encephalopathy and is characterized by progressive neurodegeneration. Treatment options for this condition remain limited to date. Nonetheless, two lines of research endeavor in the past decade have shown encouraging results worthy of further investigations. First, therapeutic hypoxia appears to improve neurological outcomes, which is somewhat counterintuitive but supported by preclinical evidence. Furthermore, nicotinic acid or nicotinamide riboside could be an adjunctive therapy that enhances the neuroprotective effect of hypoxia. Second, preclinical studies and preliminary clinical experience suggest that sildenafil is potentially disease-modifying for Leigh syndrome. Sildenafil has already been used to treat pulmonary hypertension, and its repurposing for Leigh syndrome has been endorsed by European Medicines Agency. This perspective aims to raise awareness about these progresses, as well as to call for more clinical studies to ensure safe and effective implementation of these treatment approaches in clinical practice.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":" ","pages":"4-6"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573281","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":"Enthusiasm meets opportunity: in memoriam of William L. Pak, 1932-2023.","authors":"Randall Shortridge","doi":"10.1080/01677063.2024.2419107","DOIUrl":"https://doi.org/10.1080/01677063.2024.2419107","url":null,"abstract":"","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":" ","pages":"1-2"},"PeriodicalIF":1.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769846","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}