Neurogenetics最新文献_第2页

Neurodegeneration with brain iron accumulation 5: report of three cases. 神经变性伴脑铁积累5：附3例报告。

IF 1.6 4区医学

Neurogenetics Pub Date : 2024-12-04 DOI: 10.1007/s10048-024-00783-7

Sheyda Khalilian, Mohadeseh Fathi, Akram Ghahghaei-Nezamabadi, Mohammad Miryounesi, Soudeh Ghafouri-Fard

引用次数: 0

Identification of a novel pathogenic gene, NDUFA3, in Leigh Syndrome through whole exome sequencing. 通过全外显子组测序鉴定Leigh综合征新的致病基因NDUFA3。

IF 1.6 4区医学

Neurogenetics Pub Date : 2024-11-28 DOI: 10.1007/s10048-024-00782-8

Bao-Guang Li, Wen-Juan Wu, Li-Hui Wang, Xin Wang, Chong Liu, Ya-Kun Du, Bao-Chi Li, Jin-Tong Hu, Su-Zhen Sun

{"title":"Identification of a novel pathogenic gene, NDUFA3, in Leigh Syndrome through whole exome sequencing.","authors":"Bao-Guang Li, Wen-Juan Wu, Li-Hui Wang, Xin Wang, Chong Liu, Ya-Kun Du, Bao-Chi Li, Jin-Tong Hu, Su-Zhen Sun","doi":"10.1007/s10048-024-00782-8","DOIUrl":"10.1007/s10048-024-00782-8","url":null,"abstract":"Background: Leigh syndrome is a common mitochondrial disorder caused by gene mutations in the nucleus and mitochondria. When building mitochondrial complex I, the main subunit ND1 combines with the Q module to form a 273 kDa complex, which then adds Ndufa3, Ndufa8, and Ndufa13 to create an intermediate product of about 283 kDa called Q/Pp-a. Although Ndufa8 and Ndufa13 have been linked to mitochondrial diseases, the role of Ndufa3 in disease development is still not fully understood.Methods: A family suspected of having Leigh syndrome was examined. Subjects (two brothers and a sister) underwent brain imaging, and their clinical symptoms were evaluated. Also, whole exome sequencing and minigene testing were performed by examining peripheral blood samples (2 ml) collected from the proband, his parents, and brothers.Results: Three affected children showed early-onset symptoms, including abnormalities in muscle tone and delayed motor and language development. Symptoms were relatively mild. The second child of the second pregnancy experienced worsened muscle tone abnormalities after injury, slow wound healing, and sustained increased muscle tone up to a year after wound closure. His brain scans revealed lesions in the basal ganglia and brainstem, consistent with Leigh syndrome diagnosis. Genetic analysis identified compound heterozygous mutations in the Ndufa3 gene in all affected family members.Conclusion: This is the first report of a family affected by Leigh syndrome associated with mutations in the Ndufa3 gene. Our analyses of clinical symptoms, radiological scans, and genetic investigations broaden our understanding of Ndufa3 gene mutations and their role in the development of Leigh syndrome.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"13"},"PeriodicalIF":1.6,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808764","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

Three Iranian patients with rare subtypes of hereditary spastic paraplegia (HSP): SPG76, SPG56, and SPG69. 三名患有罕见亚型遗传性痉挛性截瘫（HSP）的伊朗患者：SPG76、SPG56 和 SPG69。

IF 1.6 4区医学

Neurogenetics Pub Date : 2024-11-28 DOI: 10.1007/s10048-024-00789-1

Zahra Sadr, Aida Ghasemi, Mohammad Rohani, Hamid Reza Khorram Khorshid, Mohammad Reza Habibi-Kavashkohie, Yusuf Mohammadi, Afagh Alavi

{"title":"Three Iranian patients with rare subtypes of hereditary spastic paraplegia (HSP): SPG76, SPG56, and SPG69.","authors":"Zahra Sadr, Aida Ghasemi, Mohammad Rohani, Hamid Reza Khorram Khorshid, Mohammad Reza Habibi-Kavashkohie, Yusuf Mohammadi, Afagh Alavi","doi":"10.1007/s10048-024-00789-1","DOIUrl":"https://doi.org/10.1007/s10048-024-00789-1","url":null,"abstract":"Some subtypes of hereditary spastic paraplegia (HSP), especially with autosomal recessive inheritance (AR-HSP), have been reported rarely. In this study, we report the clinical features and molecular results of three unrelated Iranian patients with rare subtypes of HSP, including SPG76, SPG56, and SPG69; thereafter, we compare them to other reported cases. Three patients who were clinically diagnosed with HSP and born to consanguineous parents underwent molecular assessment by whole-exome sequencing (WES), followed by Sanger sequencing and co-segregation analysis. Two patients carried biallelic pathogenic variants in CAPN1, or CYP2U1, resulting in SPG76, and SPG56, respectively. Additionally, another patient presented with a variant of uncertain significance (VUS) in the gene associated with SPG69, known as RAB3GAP2. Variants of CAPN1 and RAB3GAP2 are novel while the CYP2U1 variant has been previously reported. The patient with the RAB3GAP2 variant is the second reported SPG69 case. Our findings emphasize that the rare forms of AR-HSP may be more prevalent in communities with a high rate of consanguineous marriages, and WES can be a highly effective tool for identifying pathogenic variants in these communities. Also, the CYP2U1 variant seems to be a founder mutation because it was previously reported in 8 patients of three families from the Middle East. These results expand the variant spectrum of the CAPN1 and RAB3GAP2 genes. Also, given the association of variants in CAPN1 and RAB3GAP2 with a diverse array of phenotypes, we propose the use of the terms \"CAPN1-related disorders\" and \"RAB3GAP2-related disorders\" as alternatives to HSP76 and HSP69, respectively.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"12"},"PeriodicalIF":1.6,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741467","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

Giant axonal neuropathy: a rare inherited neuropathy with a novel mutation. 巨轴突性神经病：一种罕见的遗传性神经病，伴有新型突变。

IF 1.6 4区医学

Neurogenetics Pub Date : 2024-11-27 DOI: 10.1007/s10048-024-00790-8

Bita Poorshiri, Neda Jabbarpour, Mohammad Barzegar, Mortaza Bonyadi, Zakiyeh Ebadi

{"title":"Giant axonal neuropathy: a rare inherited neuropathy with a novel mutation.","authors":"Bita Poorshiri, Neda Jabbarpour, Mohammad Barzegar, Mortaza Bonyadi, Zakiyeh Ebadi","doi":"10.1007/s10048-024-00790-8","DOIUrl":"10.1007/s10048-024-00790-8","url":null,"abstract":"We present a 7.5-year-old boy born to a family from the Iranian Azeri Turkish ethnic group with a consanguineous marriage who presents with a unique set of symptoms, suggesting Giant Axonal Neuropathy. He achieved independent walking at age 3 years, with frequent falling during running. Physical and neurological examinations reveal curly blond hair, generalized muscle atrophy, slow speech and difficulty swallowing solid food, foot drop, pes cavus, hammertoe deformities; reduced deep tendon reflexes, clumsy gait, impaired sense of position, and intention tremors.This comprehensive report significantly expands the clinical and mutational spectrum of Giant Axonal Neuropathy. Whole Exome Sequencing (WES) analysis revealed a novel homozygous variant (NC_000016.10(NM_022041.3):c.2T > C) in the GAN gene, confirmed by Sanger sequencing. Segregation analysis showed that the parents were heterozygous for the variant. The variant was absent in a cohort of 430 healthy individuals from the same ethnic group and in other published population databases such as GenomAD and the 1000 Genome. The clinical manifestations, segregation analysis, population study, and bioinformatics analysis collectively confirm the pathogenicity of variant.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"11"},"PeriodicalIF":1.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734682","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

Nutrigenomics and neurological disorders: exploring diet-brain interactions for cognitive health. 营养基因组学与神经系统疾病：探索饮食与大脑的相互作用，促进认知健康。

IF 1.6 4区医学

Neurogenetics Pub Date : 2024-11-26 DOI: 10.1007/s10048-024-00791-7

Atifa Waheed, Maliha Ghaffar, Samavia Mustafa, Anam Abbas, Sana Khan, Ahmad Waheed, Hina Naz

引用次数: 0

Clinical and genetic diversity in Iranian individuals with RAPSN-related congenital myasthenic syndrome. 伊朗 RAPSN 相关先天性肌无力综合征患者的临床和遗传多样性。

IF 1.6 4区医学

Neurogenetics Pub Date : 2024-11-26 DOI: 10.1007/s10048-024-00787-3

Aida Ghasemi, Seyed Jalaleddin Hadei, Sara KamaliZonouzi, Amene Shahrokhi, Hossein Najmabadi, Shahriar Nafissi

{"title":"Clinical and genetic diversity in Iranian individuals with RAPSN-related congenital myasthenic syndrome.","authors":"Aida Ghasemi, Seyed Jalaleddin Hadei, Sara KamaliZonouzi, Amene Shahrokhi, Hossein Najmabadi, Shahriar Nafissi","doi":"10.1007/s10048-024-00787-3","DOIUrl":"https://doi.org/10.1007/s10048-024-00787-3","url":null,"abstract":"Congenital myasthenic syndromes (CMSs) are genetic disorders affecting motor function with variable symptoms. RAPSN-related CMS, caused by mutations in the RAPSN gene, leads to muscle weakness. Accurate diagnosis is essential for proper management. This study aims to analyze six Iranian families affected by RAPSN-CMS, focusing on clinical manifestations, genetic variants, treatment response, and outcomes. Clinical assessments, genetic analysis, and whole-exome sequencing were performed on the six families to identify RAPSN gene mutations. The study examined symptoms, disease severity, age of onset, treatment response, and outcomes. Treatment with pyridostigmine and salbutamol was given to assess its effectiveness. Three homozygous known variants in RAPSN gene were identified: c.491G > A in three families, c.264 C > A in two families, and c.-210 A > G in one family. Clinical assessments showed diversity in symptoms and treatment responses. Pyridostigmine and salbutamol treatment improved symptoms and quality of life. This study highlights the significance of molecular diagnosis for RAPSN-related congenital myasthenic syndromes (CMS) in Iran, marking the first comprehensive genetic analysis in the region. The identification of specific pathogenic variants underscores the unique genetic landscape of local patients. Furthermore, our long-term follow-up revealed variable treatment responses, emphasizing the need for personalized care strategies. The clinical variability among patients with identical mutations necessitates a multidisciplinary approach for effective management. By enhancing genetic awareness and refining follow-up methods, we aim to improve diagnosis accuracy and interventions, fostering better outcomes for affected families in the Iranian population.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"9"},"PeriodicalIF":1.6,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717910","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

Analysis of Alzheimer's disease associated deleterious non-synonymous single nucleotide polymorphisms and their impacts on protein structure and function by performing in-silico methods. 通过内科学方法分析与阿尔茨海默病相关的有害非同义单核苷酸多态性及其对蛋白质结构和功能的影响。

IF 1.6 4区医学

Neurogenetics Pub Date : 2024-11-26 DOI: 10.1007/s10048-024-00786-4

Betul Akcesme, Nadia Islam, Delila Lekic, Raisa Cutuk, Nejla Basovic

{"title":"Analysis of Alzheimer's disease associated deleterious non-synonymous single nucleotide polymorphisms and their impacts on protein structure and function by performing in-silico methods.","authors":"Betul Akcesme, Nadia Islam, Delila Lekic, Raisa Cutuk, Nejla Basovic","doi":"10.1007/s10048-024-00786-4","DOIUrl":"https://doi.org/10.1007/s10048-024-00786-4","url":null,"abstract":"Alzheimer's disease (AD) is a neurodegenerative disorder that is presented with a progressive loss of memory, a decline in cognitive abilities and multiple changes in behavior. Its pathogenicity has been linked to genetic factors in approximately 60-80% of the cases specifically APOE gene family and as well as other gene families. This study utilized advanced computational biology methods to analyze AD-associated nsSNPs extracted from the NHGRI-EBI GWAS Catalog. Ensembl Variant Effect Predictor (VEP) is used to annotate the variants associated with AD. Annotated missense variants were subjected to PolyPhen-2, SNPs&Go, PredictSNP servers which were used to predict pathogenicity of selected missense variants by protein sequence information. DynaMut and DUET servers were applied to determine protein stability due to the amino acid change by integrating protein structure information. Missense variations associated with AD were annotated to 26 proteins and further analyzed in our study. Following rigorous data filtration steps, 15 candidate variants (13 proteins) were identified and subjected to sequence and structure-based analysis. Finally in this in-silico study, five deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) were identified in ACKR2(V41A), APOE(R176C), ATP8B4(G395S), LAMB2(E987K), and TOMM40(R239W), and these findings were subsequently backed-up by existing in-vivo and in-vitro literature. This study not only provides invaluable insight into the intricate pathogenic mechanisms underlying AD but also offers a distinctive perspective that paves the way for future, more comprehensive investigations aimed at unraveling the molecular intricacies responsible for the development and progression of AD. Nonetheless, it is imperative that further rigorous in vivo and in vitro experiments are conducted to validate and expand upon the findings presented here.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"8"},"PeriodicalIF":1.6,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717909","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

Mild neurodevelopmental disorder due to reduced SHMT2 enzymatic activity caused by novel compound heterozygous variants: expanding the phenotypic spectrum. 新型复合杂合变体导致的 SHMT2 酶活性降低引起的轻度神经发育障碍：扩展表型谱。

IF 1.6 4区医学

Neurogenetics Pub Date : 2024-11-26 DOI: 10.1007/s10048-024-00784-6

Hu Pan, Mei He, Xuan Luo, Juanli Hu, Xiao Mao, Yong Cheng, Zhen Liu

引用次数: 0

Epigenetic dysregulation in glioblastoma: potential pathways to precision medicine. 胶质母细胞瘤的表观遗传失调：精准医疗的潜在途径。

IF 1.6 4区医学

Neurogenetics Pub Date : 2024-11-25 DOI: 10.1007/s10048-024-00793-5

Vijeta Prakash, Reema Gabrani

引用次数: 0

Understanding pathophysiology in fragile X syndrome: a comprehensive review. 了解脆性 X 综合征的病理生理学：全面综述。