Journal of neurogenetics最新文献

{"title":"Identification and bioinformatics analysis of a novel variant in the <i>HERC2</i> gene in a patient with intellectual developmental disorder.","authors":"Asal Asghari Sarfaraz, Neda Jabbarpour, Mortaza Bonyadi, Mohammad Khalaj-Kondory","doi":"10.1080/01677063.2024.2365634","DOIUrl":"10.1080/01677063.2024.2365634","url":null,"abstract":"<p><p>HERC2-associated neurodevelopmental-disorders(NDD) encompass a cluster of medical conditions that arise from genetic mutations occurring within the <i>HERC2</i> gene. These disorders can manifest a spectrum of symptoms that impact the brain and nervous system, including delayed psychomotor development, severe mental retardation, seizures and autistic features. Whole-Exome-Sequencing(WES) was performed on a ten-year-old male patient referred to the genetic center for genetic analysis. Blood samples were collected from the proband, his parents, and his sister to extract DNA. PCR-Sanger-sequencing was utilized to validate the findings obtained from WES. In order to obtain a more thorough understanding of the impact of the mutation, an extensive analysis was conducted using bioinformatics tools. WES data analysis identified a homozygous single nucleotide change(C > T) at position c14215 located in exon ninety-two of the <i>HERC2</i> gene (NC_000015.10(NM_004667.6):c.14215C > T). The absence of this mutation among our cohort composed of four hundred normal healthy adults from the same ethnic group, and its absence in any other population database, confirms the pathogenicity of the mutation. This study revealed that the substitution of arginine with a stop codon within the Hect domain caused a premature stop codon at position 4739(p.Arg4739Ter). This mutation significantly results in the production of a truncated HERC2 protein with an incomplete HECT domain. In the final stage of ubiquitin attachment, HECT E3 ubiquitin ligases play a catalytic role by creating a thiolester intermediate using their conserved catalytic cysteine (Cys4762). This intermediate is formed before ubiquitin is transferred to a substrate protein. The truncation of the HERC2 protein is expected to disrupt its ability to perform this function, which could potentially hinder important regulatory processes related to the development and maintenance of synapses. The identification of a novel pathogenic variant, NC_000015.10(NM_004667.6):c.14215C > T, located within the ninety-two exon of the <i>HERC2</i> gene, is notable for its association with an autosomal recessive inheritance pattern in cases of Intellectual Developmental Disorder(IDD). In the end, this variant could potentially play a part in the underlying mechanisms leading to the onset of intellectual developmental disorder.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":" ","pages":"19-25"},"PeriodicalIF":1.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331183","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 heterogeneity within a consanguineous family involving TTPA and SETX genes","authors":"Cyrine Jeridi, Amine Rachdi, Fatma Nabli, Zacharia Saied, Rania Zouari, Dina Ben Mohamed, Mariem Ben Said, Saber Masmoudi, Samia Ben Sassi, Rim Amouri","doi":"10.1080/01677063.2023.2281916","DOIUrl":"https://doi.org/10.1080/01677063.2023.2281916","url":null,"abstract":"Autosomal recessive cerebellar ataxias (ARCA) constitute a highly heterogeneous group of progressive neurodegenerative disorders that typically occur prior to adulthood. Despite some clinical resem...","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"9 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138716622","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":"Knockdown of circ_CLIP2 regulates the proliferation, metastasis and apoptosis of glioma cells through miR-641/EPHA3/STAT3 axis.","authors":"Huibing Li,&nbsp;Xin Jin,&nbsp;Mingyao Lai,&nbsp;Yongshi Li,&nbsp;Ruixing Li,&nbsp;Huihui Yang,&nbsp;Baoying Yang","doi":"10.1080/01677063.2023.2199067","DOIUrl":"10.1080/01677063.2023.2199067","url":null,"abstract":"<p><p>A great amount of reaches have confirmed that circular RNAs (circRNAs) are novel regulators in glioma progression. Here, our work aimed to probe the specific role of circ_CLIP2 in glioma. The mRNA and protein expressions were analyzed by qRT-PCR and western blot, respectively. Cell viability, migration, invasion and apoptosis were examined by MTT assay, tranwell and flow cytometry assays, respectively. Moreover, the binding relationships between circ_CLIP2, microRNA (miR)-641 and erythropoietin-producing human hepatocellular (Eph)A3 were verified by dual luciferase reporter gene assay and/or RIP assay. The following data showed that circ_CLIP2 and EPHA3 were markedly increased in glioma tissues and cells, while miR-647 was downregulated. Gain- and loss-of-function experiments discovered that circ_CLIP2 knockdown remarkably inhibited cell proliferation, migration and invasion and promoted cell apoptosis of glioma cells, while these effects of circ_CLIP2 knockdown were abolished by miR-641 inhibition. Circ_CLIP2 was proved as a sponge of miR-641 to competitively upregulate EPHA3 expression. In addition, EPHA3 overexpression could abolish the inhibitory effects of miR-641 overexpression on the malignant behaviors of glioma cells by activating the signal transducer and activator of transcription 3 (STAT3). These findings elucidated that circ_CLIP2 knockdown suppressed glioma development by regulation of the miR-641/EP HA3/STAT3 axis, which provided a novel mechanism for understanding the pathogenesis of glioma.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":" ","pages":"93-102"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9400133","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":"Neural stem cell-derived exosomal FTO protects neuron from microglial inflammatory injury by inhibiting microglia NRF2 mRNA m6A modification.","authors":"Zhiyong Li, Zhenggang Chen, Jun Peng","doi":"10.1080/01677063.2023.2259995","DOIUrl":"10.1080/01677063.2023.2259995","url":null,"abstract":"<p><p>Ischemic stroke (IS) can cause neuronal cell loss and function defects. Exosomes derived from neural stem cells (NSC-Exos) improve neural plasticity and promote neural function repair following IS. However, the potential mechanism remains unclear. In this study, NSC-Exos were characterized and co-cultured with microglia. We found that NSC-Exos increased NRF2 expression in oxygen-glucose deprivation/reoxygenation and LPS-induced microglia and converted microglia from M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype. NSC-Exos reduced m6A methylation modification of nuclear factor erythroid 2-related factor 2 (NRF2) mRNA via obesity-associated gene (FTO). Furthermore, NSC-Exos reduced the damage to neurons caused by microglia's inflammatory response. Finally, the changes in microglia polarization and neuron damage caused by FTO knockdown in NSE-Exos were attenuated by NRF2 overexpression in microglia. These findings revealed that NSC-Exos promotes NRF2 expression and M2 polarization of microglial via transferring FTO, thereby resulting in neuroprotective effects.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":" ","pages":"103-114"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41133141","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 <i>DST</i> gene in neurobiology.","authors":"Robert Lalonde, Catherine Strazielle","doi":"10.1080/01677063.2024.2319880","DOIUrl":"10.1080/01677063.2024.2319880","url":null,"abstract":"<p><p><i>DST</i> is a gene whose alternative splicing yields epithelial, neuronal, and muscular isoforms. The autosomal recessive <i>Dst^dt</i> (<i>dystonia musculorum</i>) spontaneous mouse mutation causes degeneration of spinocerebellar tracts as well as peripheral sensory nerves, dorsal root ganglia, and cranial nerve ganglia. In addition to <i>Dst^dt</i> mutants, axonopathy and neurofilament accumulation in perikarya are features of two other murine lines with spontaneous <i>Dst</i> mutations, targeted <i>Dst</i> knockout mice, <i>Dst</i>Tg4 transgenic mice carrying two deleted <i>Dst</i> exons, <i>Dst</i>^Gt mice with trapped actin-binding domain-containing isoforms, and conditional Schwann cell-specific <i>Dst</i> knockout mice. As a result of nerve damage, <i>Dst^dt</i> mutants display dystonia and ataxia, as seen in several genetically modified models and their motor coordination deficits have been quantified along with the spontaneous <i>Dst</i> nonsense mutant, the conditional Schwann cell-specific <i>Dst</i> knockout, the conditional <i>Dst</i>^Gt mutant, and the Dst-b isoform specific <i>Dst</i> mutant. Recent findings in humans have associated <i>DST</i> mutations of the Dst-b isoform with hereditary sensory and autonomic neuropathies type 6 (HSAN-VI). These data should further encourage the development of genetic techniques to treat or prevent ataxic and dystonic symptoms.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":" ","pages":"131-138"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140094230","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":"Yin Yang 1 suppresses apoptosis and oxidative stress injury in SH-SY5Y cells by facilitating NR4A1 expression.","authors":"Qin Kang, Wen Chai, Jun Min, Xinhui Qu","doi":"10.1080/01677063.2023.2270745","DOIUrl":"10.1080/01677063.2023.2270745","url":null,"abstract":"<p><p>Oxidative stress plays a significant role in the development of Parkinson's disease (PD). Previous studies implicate nuclear receptor subfamily 4 group A member 1 (NR4A1) in oxidative stress associated with PD. However, the molecular mechanism underlying the regulation of NR4A1 expression remains incompletely understood. In the present study, a PD cell model was established by using 1-methyl-4-phenylpyridinium (MPP⁺) in SH-SY5Y cells. Cell viability and apoptosis were assessed by using CCK-8 assay and flow cytometry, respectively. The activities of LDH and SOD, and ROS generation were used as an indicators of oxidative stress. ChIP-PCR was performed to detect the interaction between Yin Yang 1 (YY1) and the <i>NR4A1</i> promoter. MPP⁺ treatment inhibited SH-SY5Y cell viability in a dose- and time-dependent manner. NR4A1 and YY1 expression were decreased in MPP⁺-treated SH-SY5Y cells. Increasing NR4A1 or YY1 alleviated MPP⁺-induced apoptosis and oxidative stress in SH-SY5Y cells, whereas reduction of NR4A1 aggravated MPP⁺-induced cell injury. Transcription factor YY1 facilitated NR4A1 expression by binding with <i>NR4A1</i> promoter. In addition, in MPP⁺-treated SH-SY5Y cells, the inhibition of NR4A1 to apoptosis and oxidative stress was further enhanced by overexpression of YY1. The reduction of NR4A1 led to an elevation of apoptosis and oxidative stress in MPP⁺-induced SH-SY5Y cells, and this effect was partially reversed by the overexpression of YY1. In conclusion, YY1 suppresses MPP⁺-induced apoptosis and oxidative stress in SH-SY5Y cells by binding with <i>NR4A1</i> promoter and boosting NR4A1 expression. Our findings suggest that NR4A1 may be a candidate target for PD treatment.HIGHLIGHTSNR4A1 and YY1 are decreased in MPP⁺-treated SH-SY5Y cells.NR4A1 prevents oxidative stress and apoptosis in MPP⁺-treated SH-SY5Y cells.YY1 binds with <i>NR4A1</i> promoter and increases NR4A1 expression.YY1 enhances the inhibition of NR4A1 to SH-SY5Y cell apoptosis and oxidative stress.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":" ","pages":"115-123"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71434299","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 conserved function of Pkhd1l1, a mammalian hair cell stereociliary coat protein, in regulating hearing in zebrafish.","authors":"Stylianos Makrogkikas,&nbsp;Ruey-Kuang Cheng,&nbsp;Hao Lu,&nbsp;Sudipto Roy","doi":"10.1080/01677063.2023.2187792","DOIUrl":"10.1080/01677063.2023.2187792","url":null,"abstract":"<p><p><i>Pkhd1l1</i> is predicted to encode a very large type-I transmembrane protein, but its function has largely remained obscure. Recently, it was shown that Pkhdl1l1 is a component of the coat that decorates stereocilia of outer hair cells in the mouse ear. Consistent with this localization, conditional deletion of <i>Pkhd1l1</i> specifically from hair cells, was associated with progressive hearing loss. In the zebrafish, there are two paralogous <i>pkhd1l1</i> genes - <i>pkhd1l1α</i> and <i>pkhd1l1β.</i> Using CRISPR-Cas9 mediated gene editing, we generated loss-of-function alleles for both and show that the double mutants exhibit nonsense-mediated-decay (NMD) of the RNAs. With behavioural assays, we demonstrate that zebrafish <i>pkhd1l1</i> genes also regulate hearing; however, in contrast to <i>Pkhd1l1</i> mutant mice, which develop progressive hearing loss, the double mutant zebrafish exhibited statistically significant hearing loss even from the larval stage. Our data highlight a conserved function of <i>Pkhd1l1</i> in hearing and based on these findings from animal models, we postulate that <i>PKHD1L1</i> could be a candidate gene for sensorineural hearing loss (SNHL) in humans.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":" ","pages":"85-92"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9240088","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":"Starvation-induced sleep suppression requires the <i>Drosophila</i> brain nutrient sensor.","authors":"Yangkyun Oh,&nbsp;Greg S B Suh","doi":"10.1080/01677063.2023.2203489","DOIUrl":"https://doi.org/10.1080/01677063.2023.2203489","url":null,"abstract":"<p><p>Animals increase their locomotion activity and reduce sleep duration under starved conditions. This suggests that sleep and metabolic status are closely interconnected. The nutrient and hunger sensors in the <i>Drosophila</i> brain, including diuretic hormone 44 (DH44)-, CN-, and cupcake-expressing neurons, detect circulating glucose levels in the internal milieu, regulate the insulin and glucagon secretion and promote food consumption. Food deprivation is known to reduce sleep duration, but a potential role mediated by the nutrient and hunger sensors in regulating sleep and locomotion activity remains unclear. Here, we show that DH44 neurons are involved in regulating starvation-induced sleep suppression, but CN neurons or cupcake neurons may not be involved in regulating starvation-induced sleep suppression or baseline sleep patterns. Inactivation of DH44 neurons resulted in normal daily sleep durations and patterns under fed conditions, whereas it ablated sleep reduction under starved conditions. Inactivation of CN neurons or cupcake neurons, which were proposed to be nutrient and hunger sensors in the fly brain, did not affect sleep patterns under both fed and starved conditions. We propose that the glucose-sensing DH44 neurons play an important role in mediating starvation-induced sleep reduction.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"37 1-2","pages":"70-77"},"PeriodicalIF":1.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10171511","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 deep learning analysis of <i>Drosophila</i> body kinematics during magnetically tethered flight.","authors":"Geonil Kim,&nbsp;JoonHu An,&nbsp;Subin Ha,&nbsp;Anmo J Kim","doi":"10.1080/01677063.2023.2210682","DOIUrl":"https://doi.org/10.1080/01677063.2023.2210682","url":null,"abstract":"<p><p>Flying <i>Drosophila</i> rely on their vision to detect visual objects and adjust their flight course. Despite their robust fixation on a dark, vertical bar, our understanding of the underlying visuomotor neural circuits remains limited, in part due to difficulties in analyzing detailed body kinematics in a sensitive behavioral assay. In this study, we observed the body kinematics of flying <i>Drosophila</i> using a magnetically tethered flight assay, in which flies are free to rotate around their yaw axis, enabling naturalistic visual and proprioceptive feedback. Additionally, we used deep learning-based video analyses to characterize the kinematics of multiple body parts in flying animals. By applying this pipeline of behavioral experiments and analyses, we characterized the detailed body kinematics during rapid flight turns (or saccades) in two different visual conditions: spontaneous flight saccades under static screen and bar-fixating saccades while tracking a rotating bar. We found that both types of saccades involved movements of multiple body parts and that the overall dynamics were comparable. Our study highlights the importance of sensitive behavioral assays and analysis tools for characterizing complex visual behaviors.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"37 1-2","pages":"47-56"},"PeriodicalIF":1.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9784307","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":"Reduced branched-chain aminotransferase activity alleviates metabolic vulnerability caused by dim light exposure at night in <i>Drosophila</i>.","authors":"Mari Kim,&nbsp;Gwang-Ic Son,&nbsp;Yun-Ho Cho,&nbsp;Gye-Hyeong Kim,&nbsp;Sung-Eun Yun,&nbsp;Young-Joon Kim,&nbsp;Jongkyeong Chung,&nbsp;Eunil Lee,&nbsp;Joong-Jean Park","doi":"10.1080/01677063.2022.2144292","DOIUrl":"https://doi.org/10.1080/01677063.2022.2144292","url":null,"abstract":"<p><p>The rhythmic pattern of biological processes controlled by light over 24 h is termed the circadian rhythm. Disturbance of circadian rhythm due to exposure to light at night (LAN) disrupts the sleep-wake cycle and can promote cardiovascular disease, diabetes, cancer, and metabolic disorders in humans. We studied how dim LAN affects the circadian rhythm and metabolism using male <i>Drosophila</i>. Wild-type flies exposed to the dim light of 10 lux at night displayed altered 24 h sleep-wake behavior and expression patterns of circadian rhythm genes. In addition, the flies became more vulnerable to metabolic stress, such as starvation. Whole-body metabolite analysis revealed decreased amounts of branched-chain amino acids (BCAAs), such as isoleucine and valine. The dim light exposure also increased the expression of branched-chain amino acid aminotransferase (BCAT) and branched-chain α-keto acid dehydrogenase (BCKDC) enzyme complexes that regulate the metabolism of BCAAs. Flies with the <i>Bcat</i> heterozygous mutation were not vulnerable to starvation stress, even when exposed to dim LAN, and hemolymph BCAA levels did not decrease in these flies. Furthermore, the vulnerability to starvation stress was also suppressed when the <i>Bcat</i> expression level was reduced in the whole body, neurons, or fat body during adulthood using conditional GAL4 and RNA interference. Finally, the metabolic vulnerability was reversed when BCAAs were fed to wild-type flies exposed to LAN. Thus, short-term dim light exposure at night affects the expression of circadian genes and BCAA metabolism in <i>Drosophila</i>, implying a novel function of BCAAs in suppressing metabolic stress caused by disrupted circadian rhythm.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"37 1-2","pages":"25-35"},"PeriodicalIF":1.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9785853","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}