Journal of neurogenetics最新文献

{"title":"SORDD: mutation frequency and phenotype in predominantly axonal Charcot-Marie-Tooth disease of undefined genetic cause.","authors":"Annabelle Arlt, Esra Akova-Öztürk, Anja Schirmacher, Bernhard Schlüter, Stephan Rust, Gerd Meyer Zu Hörste, Heinz Wiendl, Sarah Wiethoff","doi":"10.1080/01677063.2024.2374898","DOIUrl":"10.1080/01677063.2024.2374898","url":null,"abstract":"<p><p>Pathogenic, biallelic variants in <i>SORD</i> were identified in 2020 as a novel cause for autosomal-recessive Charcot-Marie-Tooth disease (CMT) type 2, an inherited neuropathy. <i>SORD</i> codes for the enzyme sorbitol dehydrogenase. Loss of this enzyme's activity leads to an increase of sorbitol in serum. We retrospectively screened 166 patients with axonal neuropathy (predominantly CMT type 2, but including intermediate form of CMT and distal hereditary motor neuropathy (dHMN)) without identified genetic etiology for <i>SORD</i> mutations at a single large German neuromuscular center. Clinical and electrophysiology exam findings were analyzed for genotype-phenotype correlation. Five patients of the total cohort of 166 patients harbored pathogenic variants in <i>SORD</i> (3%). The homozygous frameshift variant c.757delG (p.Ala253Glnfs*27) was the most common (4/5). One additional case carried this variant on one allele only and an additional pathogenic missense variant c.458C > A (p.Ala153Asp) on the other allele. Age of onset ranged from early infancy to mid-twenties, and phenotypes comprised axonal CMT (4) and dHMN (1). Our findings strengthen the importance of screening for pathogenic variants in <i>SORD</i>, especially in patients with genetically unconfirmed axonal neuropathy, especially CMT type 2 and dHMN.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":" ","pages":"35-40"},"PeriodicalIF":1.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555029","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":"Global research landscape on the contribution of de novo mutations to human genetic diseases over the past 20 years: bibliometric analysis","authors":"Jing Guan, Xiaonan Wu, Jiao Zhang, Jin Li, Hongyang Wang, Qiuju Wang","doi":"10.1080/01677063.2024.2335171","DOIUrl":"https://doi.org/10.1080/01677063.2024.2335171","url":null,"abstract":"As the contribution of de novo mutations (DNMs) to human genetic diseases has been gradually uncovered, analyzing the global research landscape over the past 20 years is essential. Because of the l...","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"50 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140634618","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":"Meta-analysis of the association between <i>C9orf72</i> repeats and neurodegeneration diseases.","authors":"Pingfei Jin, Yong Li, Yao Li","doi":"10.1080/01677063.2024.2343672","DOIUrl":"10.1080/01677063.2024.2343672","url":null,"abstract":"<p><p>To conduct a meta-analysis investigating the relationship between the chromosome 9 open reading frame 72 (<i>C9orf72</i>) GGGGCC (G4C2) and neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). We searched the EMBASE, PubMed, Web of Science, and Cochrane databases. Twenty-seven case-control studies were included, comprising 7202 AD, 5856 PD, 644 MSA, 439 PSP, and 477 CBD cases. This study demonstrated that <i>C9orf72</i> repeat expansions (>30) were associated with AD, MSA, PSP, and CBD (AD: OR = 4.88, 95% CI = 2.71-8.78; MSA: OR = 6.98, 95% CI = 1.48-33.01; PSP: OR =10.04, 95% CI = 2.72-37.10; CBD: OR = 28.04, 95% CI = 10.17-77.31). <i>C9orf72</i> intermediate repeat expansions (20-30) were not associated with AD and MSA (AD: OR = 1.16, 95% CI = 0.39-3.45; MSA: OR = 5.65, 95% CI = 0.69-46.19), while <i>C9orf72</i> repeat expansions (>30) were not associated with the risk of PD (OR = 1.51, 95% CI = 0.55-4.17), <i>C9orf72</i> intermediate repeat expansions (20-30) were indeed associated with PD (OR = 2.43, 95% CI = 1.20-4.9). The pathological mechanism of <i>C9orf72</i> G4C2 repeat expansions differs across various NDs due to the varying number of pathogenic expansions. Measuring the number of <i>C9orf72</i> G4C2 repeats may be useful in the early-stage differential diagnosis of various NDs.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":" ","pages":"1-8"},"PeriodicalIF":1.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065895","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":"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}