Neurogenetics最新文献

{"title":"Early-onset Parkinson's disease in a patient with a rare homozygous pathogenic GBA1 variant and no Gaucher disease symptoms.","authors":"Juliana Cordovil Cotrin, Rafael Mina Piergiorge, Andressa Pereira Gonçalves, Mariana Spitz, Alexandra Lehmkuhl Gerber, Ana Paula de Campos Guimarães, Ana Tereza Ribeiro Vasconcelos, Cíntia Barros Santos-Rebouças","doi":"10.1007/s10048-025-00810-1","DOIUrl":"https://doi.org/10.1007/s10048-025-00810-1","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a multifaceted neurodegenerative disorder with both non-motor and motor symptoms. Variants in the glucosylceramidase beta 1 (GBA1) gene are the strongest genetic risk factor for PD, while homozygous or compound heterozygous variants in this gene classically cause Gaucher disease (GD). This study presents an early-onset PD patient with a homozygous GBA1 deletion. Whole-exome sequencing (WES) was performed, and the identified variant was validated via Sanger sequencing. The variant was classified according to ACMG guidelines and ClinGen updates. The patient, a Brazilian female of mixed ethnicity, exhibited the full spectrum of classical motor and non-motor PD symptoms without evident hallmarks of GD. The identified homozygous GBA1 variant (NM_000157.4:c.222_224del; p.T75del; rs761621516) has a very low global allele frequency (0.00003284) and is associated with reduced enzymatic activity. This variant exhibits a founder effect among individuals of African descent. This case highlights an intricate genotype-phenotype landscape for GBA1 variants, underscoring the role of homozygous GBA1 variants in PD pathogenesis.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"28"},"PeriodicalIF":1.6,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426803","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 of critical genes and drug repurposing targets in entorhinal cortex of Alzheimer's disease.","authors":"Arghavan Hosseinpouri, Khadijeh Sadegh, Zeinab Zarei-Behjani, Zeinab Dehghan, Reza Karbalaei","doi":"10.1007/s10048-025-00806-x","DOIUrl":"https://doi.org/10.1007/s10048-025-00806-x","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a slow brain degeneration disorder in which the accumulation of beta-amyloid precursor plaque and an intracellular neurofibrillary tangle of hyper-phosphorylated tau proteins in the brain have been implicated in neurodegeneration. In this study, we identified the most important genes that are unique and sensitive in the entorhinal region of the brain to target AD effectively. At first, microarrays data are selected and constructed protein-protein interaction network (PPIN) and gene regulatory network (GRN) from differentially expressed genes (DEGs) using Cytoscape software. Then, networks analysis was performed to determine hubs, bottlenecks, clusters, and signaling pathways in AD. Finally, critical genes were selected as targets for repurposing drugs. Analyzing the constructed PPIN and GRN identified CD44, ELF1, HSP90AB1, NOC4L, BYSL, RRP7A, SLC17A6, and RUVBL2 as critical genes that are dysregulated in the entorhinal region of AD suffering patients. The functional enrichment analysis revealed that DEG nodes are involved in the synaptic vesicle cycle, glutamatergic synapse, PI3K-Akt signaling pathway, retrograde endocannabinoid signaling, endocrine and other factor-regulated calcium reabsorption, ribosome biogenesis in eukaryotes, and nicotine addiction. Gentamicin, isoproterenol, and tumor necrosis factor are repurposing new drugs that target CD44, which plays an important role in the development of AD. Following our model validation using the existing experimental data, our model based on previous experimental reports suggested critical molecules and candidate drugs involved in AD for further investigations in vitro and in vivo.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"27"},"PeriodicalIF":1.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384161","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":"Retraction Note: Impact of flexible assertive community treatment model (FACT) on community rehabilitation of schizophrenia in Southern China.","authors":"Yinglin Zhao, Shaoxiong Zheng, Handi Zhang, Yinnan Zhang, Zidong Wang, Qingjun Huang","doi":"10.1007/s10048-025-00809-8","DOIUrl":"https://doi.org/10.1007/s10048-025-00809-8","url":null,"abstract":"","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"26"},"PeriodicalIF":1.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257405","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 and expressional insights into the association of TRAPPC10 variants with neurodevelopmental disorders.","authors":"Peng-Yu Wang, Wen-Hui Liu, Yu-Jie Gu, Sheng Luo","doi":"10.1007/s10048-025-00804-z","DOIUrl":"https://doi.org/10.1007/s10048-025-00804-z","url":null,"abstract":"","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"25"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076386","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":"Correction to: Gene-gene interaction network analysis indicates CNTN2 is a candidate gene for idiopathic generalized epilepsy.","authors":"Zhi-Jian Lin, Jun-Wei He, Sheng-Yin Zhu, Li-Hong Xue, Jian-Feng Zheng, Li-Qin Zheng, Bi-Xia Huang, Guo-Zhang Chen, Peng-Xing Lin","doi":"10.1007/s10048-025-00802-1","DOIUrl":"https://doi.org/10.1007/s10048-025-00802-1","url":null,"abstract":"","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"24"},"PeriodicalIF":1.6,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054292","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":"Phenotypic variability in progressive encephalopathy with brain atrophy and thin corpus callosum: insights from two families.","authors":"Busra Aynekin, Sinan Akbaş, Ayten Gulec, Ummu Gulsum Ozgul Gumus, Abdullah Emre Guner, Stephanie Efthymiou, Henry Houlden, Gözde Yesil Sayın, Huseyin Per","doi":"10.1007/s10048-025-00799-7","DOIUrl":"https://doi.org/10.1007/s10048-025-00799-7","url":null,"abstract":"<p><p>The cytoskeleton, composed of microtubules, intermediate filaments and actin filaments is vital for various cellular functions, particularly within the nervous system, where microtubules play a key role in intracellular transport, cell morphology, and synaptic plasticity. Tubulin-specific chaperones, including tubulin folding cofactors (TBCA, TBCB, TBCC, TBCD, TBCE), assist in the proper formation of α/β-tubulin heterodimers, essential for microtubule stability. Pathogenic variants in these chaperone-encoding genes, especially TBCD, have been linked to Progressive Encephalopathy with Brain Atrophy and Thin Corpus Callosum (PEBAT, OMIM #604,649), a severe neurodevelopmental disorder. We report three cases from two consanguineous families with varying clinical presentations of PEBAT syndrome due to homozygous pathogenic variants in the TBCD. In Family 1, two siblings (F1C1 and F1C2) harboring the homozygous c.2314C > T, p.(Arg772Cys) variant exhibited severe neurodevelopmental regression, spastic tetraplegia, seizures, and brain atrophy. In contrast, Family 2, Case 3 (F2C3), with the homozygous c.230A > G, p.(His77Arg) variant, presented a milder phenotype, including absence seizures, slight developmental delay, and less pronounced neuroanatomical abnormalities. These findings contribute to the expanding phenotypic spectrum of PEBAT and suggesting that modifier genes or epigenetic factors may influence disease severity.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"23"},"PeriodicalIF":1.6,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034794","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 molecular mechanism of nitric oxide in memory consolidation and its role in the pathogenesis of memory-related disorders.","authors":"Zainab I Bahdar, Ejlal Abu-El-Rub, Rawan Almazari, Ayman Alzu'bi, Raed M Al-Zoubi","doi":"10.1007/s10048-025-00803-0","DOIUrl":"10.1007/s10048-025-00803-0","url":null,"abstract":"<p><p>Memory is a dynamic process of encoding, storing, and retrieving information. It includes sensory, short-term, and long-term memory, each with unique characteristics. Nitric oxide (NO) is a biological messenger synthesized on demand by neuronal nitric oxide synthase (nNOS) through a biochemical process initiated by glutamate binding to NMDA receptors, causing membrane depolarization and calcium influx. NO is known to regulate many signaling pathways including those related to memory consolidation. To throw light on the precise molecular mechanism of nitric oxide (NO) in memory consolidation and the possibility of targeting NO pathways as a therapeutic approach to scale down cognitive impairments. We conducted a search of the PubMed MEDLINE database, maintained by the US National Library of Medicine. The search strategy utilized Medical Subject Headings (MeSH) terms, including \"nitric oxide and memory,\" \"nitric oxide synthesis in the brain,\" \"nitric oxide and Alzheimer's,\" \"nitric oxide and Parkinson's,\" and \"nitric oxide, neurodegenerative disorders, and psychiatric disorders.\" Additionally, relevant keywords such as \"nitric oxide,\" \"memory,\" and \"cognitive disorders\" were employed. We included the most recent preclinical and clinical studies pertinent to the review topic and limited the selection to articles published in English. NO exerts its role in memory consolidation by diffusing between neurons to promote synaptic plasticity, especially long-term potentiation (LTP). It acts as a retrograde messenger, neurotransmitter release modulator, and synaptic protein modifier. The dysregulation of NO balance in the brain can contribute to the pathogenesis of various neurodegenerative diseases, particularly Alzheimer's, Parkinson's, and psychiatric disorders. The disturbance in NO signaling is strongly correlated with synaptic signaling dysfunction and oxidative stress. NO plays a fundamental role in memory consolidation, and its dysregulation contributes to cognitive impairment-a hallmark of numerous neurodegenerative and psychiatric disorders. Future research should aim to deepen our understanding of the mechanisms underlying NO's involvement in memory consolidation and to explore therapeutic strategies targeting the NO pathway to mitigate cognitive decline in affected individuals.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"22"},"PeriodicalIF":1.6,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034798","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":"Neuroinflammation and neurodegeneration in Huntington's disease: genetic hallmarks, role of metals and organophosphates.","authors":"Omkar Kumar Kunwar, Shamsher Singh","doi":"10.1007/s10048-025-00801-2","DOIUrl":"https://doi.org/10.1007/s10048-025-00801-2","url":null,"abstract":"<p><p>Huntington's disease (HDs) is a fatal, autosomal dominant, and hereditary neurodegenerative disorder characterized by progressive motor dysfunction, cognitive decline, and psychiatric disturbances. HD is well linked to mutation in the HTT gene, which leads to an abnormal expansion of trinucleotide CAG repeats, resulting in the production of the mHTT protein and responsible for abnormally long poly-Q tract. These abnormal proteins disrupt cellular processes, including neuroinflammation, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction, ultimately leading to selective neuronal loss in the brain. Epidemiological studies reveal significant regional variability in HDs prevalence, with the highest rates observed in North America and the lowest in Africa. In addition to genetic factors, environmental influences such as exposure to metals, and chemicals, and lifestyle factors like alcohol and tobacco use may exacerbate disease progression. This review explores the molecular mechanisms underlying HDs and emphasize the role of neuroinflammatory mediators and environmental factors, in HD research. Understanding these complex interactions is crucial for developing targeted interventions that can slow or halt the progression of this devastating disease.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"21"},"PeriodicalIF":1.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017118","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":"Neuronal ceroid lipofuscinosis 11 (CLN11) presenting with early-onset cone-rod dystrophy and learning difficulties.","authors":"Gustavo Maximiano-Alves, Renata do Amaral Moreto Caravelas, Trajano Aguiar Pires Gonçalves, Kelvin Ferrari Corniani, Júlio Cesar Nather, Camila Vasconcelos Geraldi-Tomaselli, Rodrigo Siqueira Soares Frezatti, Regina Maria França Fernandes, Antônio Carlos Dos Santos, Wilson Marques, Pedro José Tomaselli","doi":"10.1007/s10048-025-00800-3","DOIUrl":"https://doi.org/10.1007/s10048-025-00800-3","url":null,"abstract":"<p><p>Neuronal Ceroid Lipofuscinosis 11 (CLN11) is an ultra-rare subtype of adult-onset Neuronal Ceroid Lipofuscinosis. Its phenotype is variable and not fully known. A 21-year-old man was evaluated in our neurogenetic outpatient clinic for early onset complex phenotype, including learning difficulties, cerebellar ataxia, cone-rod dystrophy, epilepsy, and dystonia. The patient was submitted to neurological and neuropsychological assessment, neuro-ophthalmological tests, brain MRI, EEG and whole exome sequencing. A homozygous frameshift variant (NM_002087.4: c.768_769dup; p.Gln257Profs*27) was found. Distinct type descriptions, as in this case, increase the clinical spectrum of the disease.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"20"},"PeriodicalIF":1.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985648","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":"ATXN2 polyglutamine intermediate repeats length expansions in Malaysian patients with amyotrophic lateral sclerosis (ALS).","authors":"Suzanna Edgar, Nurul Angelyn Zulhairy-Liong, Melina Ellis, Shuchi Trivedi, Danqing Zhu, Jeffrey Ochieng Odongo, Khean-Jin Goh, David Paul Capelle, Nortina Shahrizaila, Marina L Kennerson, Azlina Ahmad-Annuar","doi":"10.1007/s10048-024-00798-0","DOIUrl":"https://doi.org/10.1007/s10048-024-00798-0","url":null,"abstract":"<p><p>Intermediate CAG repeats from 29 to 33 in the ATXN2 gene contributes to the risk of amyotrophic lateral sclerosis (ALS) in European and Asian populations. In this study, 148 ALS patients of multiethnic descent: Chinese (56.1%), Malay (24.3%), Indian (12.8%), others (6.8%) and 100 neurologically normal controls were screened for the ATXN2 CAG repeat expansion. The most common repeat length in both the controls and patients was 22. No familial ALS patients were positive for the intermediate repeat sizes (29-33), while four sporadic patients (2.8%) were positive, with one harbouring a rare ATXN2 homozygous 32 repeat expansion, and a likely pathogenic variant in SPAST. All four patients had limb-onset ALS. Despite representing the smallest ethnic group in our patient cohort, three of the four patients with intermediate repeat sizes were of Indian ancestry. This study, which is the first in Malaysia and Southeast Asia, shows that ATXN2 intermediate risk expansions are relevant to ALS in these populations and will help to inform future genetic testing strategies in the clinic.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"19"},"PeriodicalIF":1.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973455","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}