Journal of neurogenetics最新文献

{"title":"The pioneering use of the PDA phenotype by Bill Pak for screening a network of phototransduction genes and the associated signaling pathways.","authors":"Baruch Minke","doi":"10.1080/01677063.2024.2335146","DOIUrl":"https://doi.org/10.1080/01677063.2024.2335146","url":null,"abstract":"","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419576","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":"Tribute to Dr. William L. Pak.","authors":"Hiroyuki Matsumoto","doi":"10.1080/01677063.2024.2366468","DOIUrl":"https://doi.org/10.1080/01677063.2024.2366468","url":null,"abstract":"","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419577","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":"Carbamazepine responsive episodic dystonia and hallucination due to pyruvate dehydrogenase E2 (DLAT) gene mutation.","authors":"Jasmine Policherla, Fatema J Serajee, Salman Rashid, A H M Mahbubul Huq","doi":"10.1080/01677063.2024.2372496","DOIUrl":"10.1080/01677063.2024.2372496","url":null,"abstract":"<p><p>Pyruvate Dehydrogenase (PDH) E2 deficiency due to Dihydrolipoamide acetyltransferase (DLAT) mutations is a very rare condition with only nine reported cases to date. We describe a 15-year-old girl with mild intellectual disability, paroxysmal dystonia and bilateral basal ganglia signal abnormalities on brain magnetic resonance imaging (MRI). Additionally, neurophysiological, imaging, metabolic and exome sequencing studies were performed. Routine metabolite testing, and GLUT1 and PRRT2 mutation analysis were negative. A repeat brain MRI revealed 'Eye-of-the-tiger-sign'. Exome sequencing identified homozygous valine to glycine alteration at amino acid position 157 in the DLAT gene. Bioinformatic and family analyses indicated that the alteration was likely pathogenic. Patient's dystonia was responsive to low-dose carbamazepine. On weaning carbamazepine, patient developed hallucinations which resolved after carbamazepine was restarted. PDH E2 deficiency due to DLAT mutation has a more benign course compared to common forms of PDH E1 deficiency due to X-linked PDHA1 mutations. All known cases of PDH E2 deficiency due to DLAT mutations share the features of episodic dystonia and intellectual disability. Our patient's dystonia and hallucinations responded well to low-dose carbamazepine.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the evidence for mitochondrial dysfunction and genetic abnormalities in the etiopathogenesis of tropical ataxic neuropathy.","authors":"Shivani Sharma, Anita Mahadevan, Gayathri Narayanappa, Monojit Debnath, Periyasamy Govindaraj, Sumanth Shivaram, Doniparthi V Seshagiri, Ramesh Siram, Akhilesh Shroti, Parayil S Bindu, Yasha T Chickabasaviah, Arun B Taly, Madhu Nagappa","doi":"10.1080/01677063.2024.2373363","DOIUrl":"10.1080/01677063.2024.2373363","url":null,"abstract":"<p><p>Tropical ataxic neuropathy (TAN) is characterised by ataxic polyneuropathy, degeneration of the posterior columns and pyramidal tracts, optic atrophy, and sensorineural hearing loss. It has been attributed to nutritional/toxic etiologies, but evidence for the same has been equivocal. TAN shares common clinical features with inherited neuropathies and mitochondrial disorders, it may be hypothesised that genetic abnormalities may underlie the pathophysiology of TAN. This study aimed to establish evidence for mitochondrial dysfunction by adopting an integrated biochemical and multipronged genetic analysis. Patients (<i>n</i> = 65) with chronic progressive ataxic neuropathy with involvement of visual and/or auditory pathways underwent deep phenotyping, genetic studies including mitochondrial DNA (mtDNA) deletion analysis, mtDNA and clinical exome sequencing (CES), and respiratory chain complex (RCC) assay. The phenotypic characteristics included dysfunction of visual (<i>n</i> = 14), auditory (<i>n</i> = 12) and visual + auditory pathways (<i>n</i> = 29). Reduced RCC activity was present in 13 patients. Mitochondrial DNA deletions were noted in five patients. Sequencing of mtDNA (<i>n</i> = 45) identified a homoplasmic variant (<i>MT-ND6)</i> and a heteroplasmic variant (<i>MT-COI</i>) in one patient each. CES (<i>n</i> = 45) revealed 55 variants in nuclear genes that are associated with neuropathy (<i>n</i> = 27), deafness (<i>n</i> = 7), ataxia (<i>n</i> = 4), and mitochondrial phenotypes (<i>n</i> = 5) in 36 patients. This study provides preliminary evidence that TAN is associated with a spectrum of genetic abnormalities, including those associated with mitochondrial dysfunction, which is in contradistinction from the prevailing hypothesis that TAN is related to dietary toxins. Analysing the functional relevance of these genetic variants may improve the understanding of the pathogenesis of TAN.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555028","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":"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}