Neurogenetics最新文献_第2页

A systematic review of hereditary neurological disorders diagnosed by whole exome sequencing in Pakistani population: updates from 2014 to November 2024. 巴基斯坦人群全外显子组测序诊断的遗传性神经疾病的系统综述：2014年至2024年11月的最新情况。

IF 1.6 4区医学

Neurogenetics Pub Date : 2025-04-03 DOI: 10.1007/s10048-025-00819-6

Riaz Ahmad, Muhammad Naeem

{"title":"A systematic review of hereditary neurological disorders diagnosed by whole exome sequencing in Pakistani population: updates from 2014 to November 2024.","authors":"Riaz Ahmad, Muhammad Naeem","doi":"10.1007/s10048-025-00819-6","DOIUrl":"10.1007/s10048-025-00819-6","url":null,"abstract":"Hereditary neurological disorders (HNDs) are a group of heterogeneous disorders characterized by significant genetic and clinical variability. HNDs are caused by dysfunction of the central or peripheral nervous system due to aberrant electrical impulses. More than 600 types of HNDs have been documented, and overall, these are the second leading cause of death worldwide. This systematic review is based on a retrospective analysis of research articles reporting HNDs diagnosed using whole exome sequencing in Pakistani families from 2014 to November 2024. Original research articles were retrieved through online surveys, notably Google Scholar, PubMed, and the Web of Science. Based on stringent selection criteria, 89 research articles and 188 variants published around 10 years were considered. Variants and research articles were cross-checked and further validated in different online databases/resources to confirm their genomic nomenclature and pathogenicity according to the ACMG guidelines. A total of 188 variants in 143 distinct genes in Pakistani families identified through whole exome sequencing have been reported to date that caused genetic and clinically heterogeneous HNDs. Consanguineous parentage was found in around 90% of cases, and approximately 91% of causative alleles were reported in homozygous state showing a predominant burden of HNDs because of blood-related marriages. The most frequent type of pathogenic variants were single nucleotide substitutions (92 missense and 39 nonsense). Among 188 variants, 76 variants were reported in 2024 and 44 variants were observed in 2023. Pakistan is the fifth most populous country in the world having an extreme prevalence of consanguinity resulting in the expression of pathogenic variants due to homozygosity. Therefore, there is a prevalence of genetic disorders particularly rare monogenic or Mendelian disorders. Next-generation sequencing approach is strongly recommended for diagnosis, early therapeutic intervention and genetic counselling.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"40"},"PeriodicalIF":1.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774939","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}

引用次数: 0

Multi-target approach to Alzheimer's disease prevention and treatment: antioxidant, anti-inflammatory, and amyloid- modulating mechanisms. 阿尔茨海默病预防和治疗的多靶点方法：抗氧化、抗炎和淀粉样蛋白调节机制。

IF 1.6 4区医学

Neurogenetics Pub Date : 2025-04-01 DOI: 10.1007/s10048-025-00821-y

Kashif Abbas, Mohd Mustafa, Mudassir Alam, Safia Habib, Waleem Ahmad, Mohd Adnan, Md Imtaiyaz Hassan, Nazura Usmani

{"title":"Multi-target approach to Alzheimer's disease prevention and treatment: antioxidant, anti-inflammatory, and amyloid- modulating mechanisms.","authors":"Kashif Abbas, Mohd Mustafa, Mudassir Alam, Safia Habib, Waleem Ahmad, Mohd Adnan, Md Imtaiyaz Hassan, Nazura Usmani","doi":"10.1007/s10048-025-00821-y","DOIUrl":"10.1007/s10048-025-00821-y","url":null,"abstract":"Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) plaque accumulation, neurofibrillary tangles, neuroinflammation, and progressive cognitive decline, posing a significant global health challenge. Growing evidence suggests that dietary polyphenols may reduce the risk and progression of AD through multifaceted neuroprotective mechanisms. Polyphenols regulate amyloid proteostasis by inhibiting β/γ-secretase activity, preventing Aβ aggregation, and enhancing clearance pathways. Their strong antioxidant properties neutralize reactive oxygen species, chelate redox-active metals, and activate cytoprotective enzymes via Nrf2 signaling. This review examines the potential therapeutic targets, signaling pathways, and molecular mechanisms by which dietary polyphenols exert neuroprotective effects in AD, focusing on their roles in modulating amyloid proteostasis, oxidative stress, neuroinflammation, and cerebrovascular health. Polyphenols mitigate neuroinflammation by suppressing NF-κB signaling and upregulating brain-derived neurotrophic factor, supporting neuroplasticity and neurogenesis. They also enhance cerebrovascular health by improving cerebral blood flow, maintaining blood-brain barrier integrity, and modulating angiogenesis. This review examines the molecular and cellular pathways through which polyphenols exert neuroprotective effects, focusing on their antioxidant, anti-inflammatory, and amyloid-modulating roles. We also discuss their influence on key AD pathologies, including Aβ deposition, tau hyperphosphorylation, oxidative stress, and neuroinflammation. Insights from clinical and preclinical studies highlight the potential of polyphenols in preventing or slowing AD progression. Future research should explore personalized dietary strategies that integrate genetic and lifestyle factors to optimize the neuroprotective effects of polyphenols.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"39"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756152","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}

引用次数: 0

Mitochondrial DNA variants revealed by whole exome sequencing: from screening to diagnosis and follow-up. 全外显子组测序揭示的线粒体DNA变异：从筛查到诊断和随访。

IF 1.6 4区医学

Neurogenetics Pub Date : 2025-03-26 DOI: 10.1007/s10048-025-00820-z

Sebastian Skoczylas, Tomasz Płoszaj, Karolina Gadzalska, Monika Gorządek, Paulina Jakiel, Ewa Juścińska, Maria Malarska, Magdalena Traczyk-Borszyńska, Hanna Biezynska, Magdalena Rychlik, Agata Pastorczak, Agnieszka Zmysłowska

{"title":"Mitochondrial DNA variants revealed by whole exome sequencing: from screening to diagnosis and follow-up.","authors":"Sebastian Skoczylas, Tomasz Płoszaj, Karolina Gadzalska, Monika Gorządek, Paulina Jakiel, Ewa Juścińska, Maria Malarska, Magdalena Traczyk-Borszyńska, Hanna Biezynska, Magdalena Rychlik, Agata Pastorczak, Agnieszka Zmysłowska","doi":"10.1007/s10048-025-00820-z","DOIUrl":"10.1007/s10048-025-00820-z","url":null,"abstract":"Mutations in mitochondrial DNA play a crucial role in several diseases, but interpreting the clinical significance of mitochondrial DNA variants is challenging due to heteroplasmy, age-related loss of variants and evolving phenotypes. The aim of study was to identify mitochondrial pathogenic variants and explore their potential future association with specific phenotypes in patients during their lifetime, for both known and novel variants. We used a Python pipeline to analyse exome sequencing data from 418 patients (median age: 15 years; 52.9% males and 47.1% females), mostly diagnosed with neurological disorders, developmental and intellectual disabilities, behavioural and sensory disorders, cardiovascular and metabolic abnormalities, renal diseases and others. Screening identified 1,000 unique variants with heteroplasmy levels greater than 10% and 192 unique variants with 1-10% heteroplasmy, excluding hypervariable regions. Among these variants, four confirmed pathogenic variants were detected according to MITOMAP (m.1555 A > G, m.3243 A > G, m.9035T > C, and m.11778G > A), each identified in one patient. The application of pathogenicity and frequency criteria led to the identification of three unique variants and one in monozygotic twin sister with low levels of heteroplasmy, which were confirmed by next-generation sequencing. Finally, one of them, the variant m.15897G > A, was recognised as likely pathogenic (PP3, PS2). Our study highlights the complexity of diagnosing mitochondrial diseases associated with mtDNA mutations and emphasises the need for a comprehensive genotype-phenotype approach to correctly identify causal variants.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"38"},"PeriodicalIF":1.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733273","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}

引用次数: 0

Repeated clear benefits of immunotherapy in a patient with Charcot-Marie-Tooth disease carrying a rare point mutation in PMP22. 携带PMP22罕见点突变的腓骨肌萎缩症患者免疫治疗的反复明确益处

IF 1.6 4区医学

Neurogenetics Pub Date : 2025-03-24 DOI: 10.1007/s10048-025-00808-9

Honami Kawai, Yoichiro Nishida, Takashi Kanda, Takanori Yokota

引用次数: 0

Genotypic and clinical phenotypic analysis of DEPDC5 gene mutations. DEPDC5基因突变的基因型和临床表型分析。

IF 1.6 4区医学

Neurogenetics Pub Date : 2025-03-18 DOI: 10.1007/s10048-025-00818-7

Baoguang Li, Zhenzhen Qu, Wenjuan Wu, Weiping Wang

{"title":"Genotypic and clinical phenotypic analysis of DEPDC5 gene mutations.","authors":"Baoguang Li, Zhenzhen Qu, Wenjuan Wu, Weiping Wang","doi":"10.1007/s10048-025-00818-7","DOIUrl":"10.1007/s10048-025-00818-7","url":null,"abstract":"Mutations in the DEPDC5 gene are inherited in an autosomal dominant manner and can lead to various clinical phenotypes, including focal seizures. While numerous case reports on DEPDC5 mutations exist, functional validation studies remain scarce. We analyzed seven cases of epilepsy or developmental disorders caused by DEPDC5 mutations, summarizing their clinical manifestations and conducting genetic analysis of the mutation sites. The age of onset in the seven patients ranged from 2 months to 4 years. Six mutation sites were identified, including three nonsense mutations: c.1443del (p.C481X), c.2512 C > T (p.R838X), and c.2620 C > T (p.R874X); one missense mutation: c.1140 C > A (p.F380L); and two splice-site mutations: c.2802-13 C > G (splicing) and c.4034-2 A > G (splicing). Among these, c.2512 C > T (p.R838X) and c.2620 C > T (p.R874X) had been previously reported, while the remaining mutations were novel. Minigene experiments confirmed that the c.4034-2 A > G mutation resulted in a slightly truncated protein.Focal seizures were the predominant symptom in six cases. Among the four patients with nonsense mutations, three (Cases 2, 4, and 5) exhibited drug-resistant epilepsy. Four out of seven patients responded effectively to lacosamide treatment. DEPDC5 mutations can cause focal seizures, with truncating mutations associated with more severe symptoms. Lacosamide may offer better therapeutic outcomes. The intronic mutation c.463 + 4 A > G (splicing) led to protein truncation and was determined to be pathogenic.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"36"},"PeriodicalIF":1.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659788","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}

引用次数: 0

A novel variant in ARSA causes a rare phenotype of infantile metachromatic leukodystrophy in a Malian family. 在一个马里家庭中，ARSA的一种新变异导致了一种罕见的婴儿异色性脑白质营养不良表型。

IF 1.6 4区医学

Neurogenetics Pub Date : 2025-03-11 DOI: 10.1007/s10048-025-00814-x

Alassane Baneye Maiga, Abdoulaye Arama, Abdoulaye Yalcouyé, Mohamed Albakaye, Ji Weizhen, Salia Bamba, Oumou Traoré, Moussa Sangaré, Mahamadou Kotioumbé, Samba Ogomaly Djimdé, Modibo K Goita, Salimata Diarra, Mustafa K Khokha, Saquib A Lakhani, Guida Landouré

引用次数: 0

Investigating the gut microbiome in schizophrenia cases versus controls: South Africa's version. 调查精神分裂症患者与对照组的肠道微生物组：南非版本。

IF 1.6 4区医学

Neurogenetics Pub Date : 2025-03-05 DOI: 10.1007/s10048-025-00816-9

Carlien Rust, Laila Asmal, Michaela O'Hare, Etheresia Pretorius, Robin Emsley, Soraya Seedat, Sian Hemmings

{"title":"Investigating the gut microbiome in schizophrenia cases versus controls: South Africa's version.","authors":"Carlien Rust, Laila Asmal, Michaela O'Hare, Etheresia Pretorius, Robin Emsley, Soraya Seedat, Sian Hemmings","doi":"10.1007/s10048-025-00816-9","DOIUrl":"10.1007/s10048-025-00816-9","url":null,"abstract":"Schizophrenia (SCZ) is a chronic and severe mental disorder with a complex molecular aetiology. Emerging evidence indicates a potential association between the gut microbiome and the development of SCZ. Considering the under-representation of African populations in SCZ research, this study aimed to explore the association between the gut microbiome and SCZ within a South African cohort. Gut microbial DNA was obtained from 89 participants (n = 41 SCZ cases; n = 48 controls) and underwent 16S rRNA (V4) sequencing. Data preparation and taxa classification were performed with the DADA2 pipeline in R studio followed by diversity analysis using QIIME2. Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC) was utilised to identify differentially abundant taxa. No statistically significant differences were observed between SCZ patients and controls in terms of alpha-diversity (Shannon q = 0.09; Simpson q = 0.174) or beta-diversity (p = 0.547). Five taxa, namely Prevotella (p = 0.037), Faecalibacterium (p = 0.032), Phascolarctobacterium (p = 0.002), Dialister (p = 0.043), and SMB53 (p = 0.012), were differentially abundant in cases compared to controls, but this observation did not survive correction for multiple testing. This exploratory study suggests a potential association between the relative abundance of Prevotella, Faecalibacterium, Phascolarctobacterium, Dialister, and SMB53 with SCZ case-control status. Given the lack of significance after correcting for multiple testing, these results should be interpreted with caution. Mechanistic studies in larger samples are warranted to confirm these findings and better understand the association between the gut microbiome and SCZ.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"34"},"PeriodicalIF":1.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558904","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}

引用次数: 0

The fourth family in the world with a novel variant in the ATP5MK gene: four siblings with complex V (ATP synthase) deficiency. 世界上第四个携带ATP5MK基因新变体的家族：四个兄弟姐妹患有复杂V （ATP合成酶）缺乏症。

IF 1.6 4区医学

Neurogenetics Pub Date : 2025-02-27 DOI: 10.1007/s10048-025-00813-y

Rojan İpek, Akçahan Akalın, Esra Habiloğlu, Salih Hattapoğlu, Ayfer Gözü Pirinççioğlu

{"title":"The fourth family in the world with a novel variant in the ATP5MK gene: four siblings with complex V (ATP synthase) deficiency.","authors":"Rojan İpek, Akçahan Akalın, Esra Habiloğlu, Salih Hattapoğlu, Ayfer Gözü Pirinççioğlu","doi":"10.1007/s10048-025-00813-y","DOIUrl":"10.1007/s10048-025-00813-y","url":null,"abstract":"Mitochondrial Complex V (ATP synthase) deficiency nuclear type 6 (MC5DN6) is a progressive neurodegenerative disorder characterized by autosomal recessive inheritance and developmental regression, particularly in gross motor skills, which manifests in early childhood. This study aims to present the discovery of a novel variant in four male siblings aged 13 years 9 months to 25 years, making this the fourth family reported globally, while also raising awareness of rare mitochondrial diseases. Four individuals from the same family were retrospectively evaluated based on their demographic, clinical, laboratory, and molecular genetic data. The mutation in the ATP5MK gene was analyzed using the exome sequencing (ES) method. The detected variation was classified according to the criteria American College of Medical Genetics. Four cases, aged between 13 years 9 months and 25 years, were analyzed. All individuals were male. While all four cases had a history of neurodegenerative disease, they also exhibited intellectual disability, muscle weakness, increased deep tendon reflexes in the lower extremities, spasticity, scoliosis, pes cavus deformity, positive Babinski reflex, abnormal gait patterns due to foot deformities, and normal cerebellar tests. Additional findings included geographic tongue (n = 2), strabismus (n = 2), nystagmus (n = 1), ophthalmoplegia (n = 2), hypertrophic upper extremity muscle body build (n = 2), keloid tissue (n = 1), and short stature (n = 3). ES of the first case identified a homozygous splice donor variant (c.87 + 1G > A) in the ATP5MK gene as a novel variant, and family screening revealed the same variant in a biallelic state in the other three siblings. The parents were confirmed as heterozygous carriers, consistent with autosomal recessive inheritance. Mitochondrial diseases can mimic a wide range of neurological disorders. They should be considered as a potential underlying cause when treatment for suspected differential diagnoses proves ineffective.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"33"},"PeriodicalIF":1.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517463","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}

引用次数: 0

Axonal motor polyneuropathy in a 13 years old Girl with a de Novo variant in ADNP. 轴突运动多发性神经病伴ADNP新发变异的13岁女孩。

IF 1.6 4区医学

Neurogenetics Pub Date : 2025-02-24 DOI: 10.1007/s10048-025-00815-w

Sara Scaccini, Carlo Alberto Cesaroni, Stefano Giuseppe Caraffi, Susanna Rizzi, Simonetta Rosato, Francesca Peluso, Carlotta Spagnoli, Anna Cavalli, Chiara Brugnoli, Giulia Scandolo, Agnese Pantani, Ivan Ivanovski, Livia Garavelli, Daniele Frattini, Carlo Fusco

{"title":"Axonal motor polyneuropathy in a 13 years old Girl with a de Novo variant in ADNP.","authors":"Sara Scaccini, Carlo Alberto Cesaroni, Stefano Giuseppe Caraffi, Susanna Rizzi, Simonetta Rosato, Francesca Peluso, Carlotta Spagnoli, Anna Cavalli, Chiara Brugnoli, Giulia Scandolo, Agnese Pantani, Ivan Ivanovski, Livia Garavelli, Daniele Frattini, Carlo Fusco","doi":"10.1007/s10048-025-00815-w","DOIUrl":"10.1007/s10048-025-00815-w","url":null,"abstract":"ADNP-Related Disorder [previously known as Helsmoortel-Van der Aa syndrome (HVDAS)] is a rare genetic condition resulting from mutations in the activity-dependent neuroprotector homeobox (ADNP) gene. The ADNP protein has multiple functions, including serving as an essential transcription factor for brain development. In addition, pathogenic variants in ADNP have been recognized as one of the most frequent monogenic causes of autism spectrum disorder (ASD) and intellectual disability. Clinical features include craniofacial dysmorphisms, congenital heart defects, gastrointestinal problems such as feeding difficulties, gastroesophageal reflux and frequent vomiting, vision problems, recurrent infections and seizures. Here we describe the novel case of a girl who came to our attention in infancy because of poor and stereotyped motor repertoire, repetitive purposeless movements, and intellectual disability. Whole exome sequencing revealed a de novo heterozygous variant in the ADNP gene, leading to the diagnosis of HVDAS at age 5 years. At the age of 12, nerve conduction velocity testing showed severe four-limb axonal motor polyneuropathy. In this article, we would like to focus on the presence of peripheral nervous system involvement associated with the pathogenic ADNP de novo variant, which may contribute to the clinical characterization of ADNP-Related Disorder.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"32"},"PeriodicalIF":1.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484922","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}

引用次数: 0

Predicting high-risk clinical missense variants of SMARCB1 in rare neurogenetic disorder schwannomatosis (nerve tumor) through sequence, structure, and molecular dynamics analyses. 通过序列、结构和分子动力学分析预测罕见神经遗传疾病神经鞘瘤病（神经肿瘤）中SMARCB1的高危临床错义变异。

IF 1.6 4区医学

Neurogenetics Pub Date : 2025-02-20 DOI: 10.1007/s10048-025-00812-z

Mitesh Patel, Reem Binsuwaidan, Malvi Surti, Nawaf Alshammari, Angum M M Ibrahim, Mohd Adnan

{"title":"Predicting high-risk clinical missense variants of SMARCB1 in rare neurogenetic disorder schwannomatosis (nerve tumor) through sequence, structure, and molecular dynamics analyses.","authors":"Mitesh Patel, Reem Binsuwaidan, Malvi Surti, Nawaf Alshammari, Angum M M Ibrahim, Mohd Adnan","doi":"10.1007/s10048-025-00812-z","DOIUrl":"10.1007/s10048-025-00812-z","url":null,"abstract":"The SMARCB1 gene codes for a key element of the SWI/SNF chromatin-modifying complex, which plays a vital role in controlling gene expression by modifying chromatin architecture. Alterations in SMARCB1 have been linked to several neurological disabilities, including schwannomatosis, a condition marked by the formation of numerous benign tumors affecting the nerve sheaths. Present study explore the effects of nonsynonymous single nucleotide polymorphisms (nsSNPs) within the SMARCB1 gene on its protein structure and functionality. We utilized both sequence-based and structure-oriented predictive models, followed by molecular dynamics simulations to examine their influence on the stability of protein and dynamic behaviour. The study focused on three key mutations: R60S, R190W, and I237M. The R190W mutation emerged as particularly significant, leading to increased protein compactness and stability due to enhanced hydrophobic interactions, although conformational flexibility was reduced. The R60S mutation was associated with destabilization of the protein structure, increasing solvent exposure and reducing hydrogen bond stability, potentially impairing the protein's function. The I237M mutation had a relatively mild impact, with only subtle changes observed in protein dynamics. These findings highlight the diverse impacts of different nsSNPs on SMARCB1, with the potential to contribute to various pathologies, including Schwannomatosis and other related disorders. This study highlights the necessity for additional experimental testing to confirm these computational findings and gain a deeper understanding of the molecular processes through which these mutations contribute to disease. The present comprehensive approach provides significant knowledge regarding the connection between SMARCB1 structure and function, providing the groundwork for potential therapeutic strategies targeting these key mutations.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"31"},"PeriodicalIF":1.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460939","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}

引用次数: 0