Global Medical Genetics最新文献

{"title":"Orchestration of Genetic Alterations in <i>PSEN1</i> and <i>PSEN2</i> Genes in Development of Alzheimer's Disease through Computational Analysis.","authors":"Asif Mir, Zainab Kamran, Wajid Iqbal","doi":"10.1055/s-0043-1777849","DOIUrl":"10.1055/s-0043-1777849","url":null,"abstract":"<p><p>Dementia is a syndrome that can cause a number of progressive illnesses that affect memory, thinking, and ability to perform everyday tasks. Alzheimer's disease (AD) is the most common cause of dementia and represents a major public health problem. AD is a progressive disease, where in early stages there is mild memory loss and in late-stage patient loses the ability to carry on a conversation. AD (for which there is no exact cause and cure known so far) is the sixth leading cause of deaths in the United States. Every 68 second someone develops AD. This study focuses on protein structure modeling of genes presenilin 1 and 2 ( <i>PSEN1</i> and <i>PSEN2</i> ) and their mutated forms (Asn141Tyr found in Chinese family, Gly34Ser identified in a Japanese patient, and Arg62Cys & Val214Leu identified in the Korean patients). It also involves wild and mutant type comparison, protein interaction studies, docking and phylogenetic history based on representative ortholog species and also sheds insight into the comparative evolutionary rates of coding sequence across various orthologs. This study gives a time and cost-effective analysis of genes ( <i>PSEN1</i> and <i>PSEN2</i> ) underlying AD and genetic alterations that drive development and causes of disease.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10777486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139425683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Analysis of <i>PAIP2B</i> to Identify a Novel Biomarker for Pancreatic Ductal Adenocarcinoma.","authors":"Yaoxian Xiang, Li Wang, Yurong Cheng, Huanjuan An, Chan Zhang, Jing Wang, Yingying Tong, Dong Yan","doi":"10.1055/s-0043-1777789","DOIUrl":"10.1055/s-0043-1777789","url":null,"abstract":"<p><p>The aim of the study was to evaluate the potential diagnostic and prognostic value of gene, Poly A-Binding Protein Interacting Protein 2B ( <i>PAIP2B</i> ) in pancreatic cancer. We used the gene expression data and clinical information of pancreatic adenocarcinoma patients from The Cancer Genome Atlas database and Gene Expression Omnibus database to analyze the expression of <i>PAIP2B</i> in pancreatic cancer samples, and validated the expression of <i>PAIP2B</i> in tumor tissue, using bioinformatics technology to explore the prognostic value of <i>PAIP2B</i> and its possible biological function. A significantly lower level of <i>PAIP2B</i> was observed in pancreatic cancer patients than in controls, and validated by immunohistochemistry. <i>PAIP2B</i> reduced the proliferation and invasion of cancer cells and had a significantly high expression in early stage. Patients with lower levels of <i>PAIP2B</i> had a significantly shorter median survival time than those with higher levels. DNA demethylation played an important role in <i>PAIP2B</i> expression. In addition, <i>PAIP2B</i> expression was significantly associated with the tumor-infiltrating immune cells, especially T cells CD8, T cells CD4 memory resting, macrophages M0, and dendritic cells resting. Our study also found that <i>PAIP2B</i> regulated miRNA function leading to disease progression in pancreatic cancer patients. Our study explored the potential value of <i>PAIP2B</i> as a biological link between prognosis and pancreatic cancer, and provided reference for the follow-up study on the role of <i>PAIP2B</i> in pancreatic cancer.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10730282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138811013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe Unilateral Microtia with Aural Atresia, Hair White Patch, Stereotypes in a Young Boy with De novo 16p13.11 Deletion: Reasons for a New Genotype-Phenotype Correlation.","authors":"Piero Pavone, Xena Giada Pappalardo, Claudia Parano, Enrico Parano, Antonio Corsello, Martino Ruggieri, Giovanni Cacciaguerra, Raffaele Falsaperla","doi":"10.1055/s-0043-1777362","DOIUrl":"10.1055/s-0043-1777362","url":null,"abstract":"<p><p><b>Background</b>  Microtia is an uncommon congenital malformation ranging from mild anatomic structural abnormalities to partial or complete absence of the ear leading to hearing impairment. Congenital microtia may present as a single malformation (isolated microtia) or sometimes associated with other congenital anomalies involving various organs. Microtia has been classified in three degrees according to the complexity of the auricular malformation and to anotia referred to the total absence of the ear. Genetic role in causing auricular malformation has been widely demonstrated, and genotype-phenotype correlation has been reported in cases of syndromic microtia. <b>Case Presentation</b>  We report here a young patient with a third degree of scale classification and aural atresia. The patient showed unspecific facial dysmorphism, speech delay, precocious teething, hair white patch, and stereotypic anomalous movements. Genetic analysis displayed a de novo 16p13.11 deletion. <b>Conclusion</b>  Microtia with aural atresia is an uncommon and severe birth defect, which affects functional and esthetic aspects, often associated with other malformations. As traumatic this disorder may be for the parents, the microtia and aural atresia are treatable, thanks to the improving and evolving surgical techniques. Based on the genetic analysis and the clinical features observed in the present case, a genotype-phenotype correlation has been proposed.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10695706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138488672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on Screening Core Biomarkers of Noise and Drug-Induced Hearing Loss Based on Transcriptomics.","authors":"Xin Qiu, Qing-Qing Jiang, Wei-Wei Guo, Ning Yu, Shi-Ming Yang","doi":"10.1055/s-0043-1777069","DOIUrl":"10.1055/s-0043-1777069","url":null,"abstract":"<p><p><b>Background</b>  Noise and drug-induced hearing loss (HL) is becoming more and more serious, but the integration and analysis based on transcriptomics and proteomics are lacking. On the one hand, this study aims to integrate existing public transcriptomic data on noise and gentamicin-induced HL. On the other hand, the study aims to establish the gentamicin and noise-induced HL model of guinea pigs, then to perform the transcriptomic and proteomic analyses. Through comprehensive analysis of the above data, we aim to screen, predict, and preliminarily verify biomarkers closely related to HL. <b>Material and Methods</b>  We screened the Gene Expression Omnibus database to obtain transcriptome data expression profiles of HL caused by noise and gentamicin, then constructed the guinea pig HL model and perform the transcriptomic and proteomic analyses. Differential expression and enrichment analysis were performed on public and self-sequenced data, and common differentially expressed genes (DEGs) and signaling pathways were obtained. Finally, we used proteomic data to screen for common differential proteins and validate common differential expression genes for HL. <b>Results</b>  By integrating the public data set with self-constructed model data set, we eventually obtained two core biomarkers of HL, which were RSAD2 and matrix metalloproteinase-3 (MMP3). Their main function is to regulate the development of sense organ in the inner ear and they are mainly involved in mitogen-activated protein kinase and phosphoinositol-3 kinase/protein kinase B signaling pathways. Finally, by integrating the proteomic data of the self-constructed model, we also found differential expression of MMP3 protein. This also preliminarily and partially verified the above-mentioned core biomarkers. <b>Conclusion and Significance</b>  In this study, public database and transcriptomic data of self-constructed model were integrated, and we screened out two core genes and various signal pathways of HL through differential analysis, enrichment analysis, and other analysis methods. Then, we preliminarily validated the MMP3 by proteomic analysis of self-constructed model. This study pointed out the direction for further laboratory verification of key biomarkers of HL, which is of great significance for revealing the core pathogenic mechanism of HL.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10695707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138488673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal Stem Cells Applications in Alzheimer's Disease","authors":"Oluwatosin Debola Oyebode, P. Tulay","doi":"10.1055/s-0043-1777087","DOIUrl":"https://doi.org/10.1055/s-0043-1777087","url":null,"abstract":"Abstract Alzheimer's disease (AD) is a neurodegenerative disorder that advances gradually and primarily impacts the hippocampus region of the brain. It is defined by a deterioration in cognitive function as well as an observable loss of memory retention. One of the major characteristics of AD is the impairment of neural generation, resulting in the depletion of neurons and synaptic connections within the nervous system. It is unfortunate to say that, at present, no definitive cure is available for AD, and no medication is effective in halting the progression of neurodegeneration associated with it. Nevertheless, it is crucial to highlight that progress has been achieved in addressing the troubling symptoms of AD. The Food and Drug Administration has granted approval for two categories of medications designed to alleviate these symptoms. The scientific community has been inspired by these advancements to investigate alternative therapeutic options, with an emphasis on stem cell therapy in particular. The main focus of this review will be on the potential for the use of a variety of mesenchymal stem cells as a treatment for AD.","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138626927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spleen-Derived CCL9 Recruits MDSC to Facilitate Tumor Growth in Orthotopic Hepatoma Mice.","authors":"Baohua Li, Wenjuan Li, Yingxue Liang, Chen Zhang, Guangyao Kong, Zongfang Li","doi":"10.1055/s-0043-1777327","DOIUrl":"10.1055/s-0043-1777327","url":null,"abstract":"<p><p><b>Objectives</b>  Spleen is involved in multiple diseases, the role of the spleen and spleen-derived factors in hepatocellular carcinoma (HCC) is still not clarified. <b>Methods</b>  In the current study, a murine H22 orthotopic hepatoma model was established. Three groups were divided: normal mice, tumor-bearing mice with spleen-preserving, and tumor-bearing mice with splenectomy. Spleen and tumor weights were recorded by weeks 1 and 2. The proportion of myeloid-derived suppressor cell (MDSC) in peripheral blood and tumor tissue was detected using flow cytometry. Protein chip assay was used to compare the differential cytokines between normal liver supernatant and tumor supernatant. The common upregulated cytokines both in spleen and tumor were focused and analyzed using gene expression profiling interactive analysis (GEPIA) database. Enzyme-linked immunosorbent assay was performed to verify the chip result, and to examine CCL9 expression before and after splenectomy. Spleen MDSC was sorted using flow cytometry, and chemotaxis assay was performed to demonstrate whether CCL9 attracted spleen MDSC. <b>Results</b>  The spleen enlarged during tumor progression, and compared with splenectomy group, there were faster tumor growth, shorter survival time, and higher proportions of MDSC in spleen-preserving group. Protein chip assay and GEPIA database revealed CCL9 was the most promising chemokine involved in HCC upregulated both in spleen and tumor tissue. CCL9 attracted MDSC in vitro, the level of CCL9 in tumor tissue was downregulated, and the percentage of MDSC was decreased after splenectomy. <b>Conclusion</b>  The results demonstrate that CCL9 may be derived from spleen; it facilitated HCC growth via the chemotaxis of MDSC, targeting CCL9 may be a promising strategy in HCC treatment.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10691915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138478849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening for Mutations in Hereditary Cancer Susceptibility Genes in a Region with High Endogamy in Brazil","authors":"Polyanna C Oliveira, Paula Correa, A. Acosta, J. Freitas, T. Machado-Lopes, T. Bomfim-Palma, Ândrea Ribeiro-Dos-Santos, Sidney Santos, Roberto Nascimento, I. Nascimento, K. Abé-Sandes","doi":"10.1055/s-0043-1777449","DOIUrl":"https://doi.org/10.1055/s-0043-1777449","url":null,"abstract":"Abstract Introduction  Cancer is a multifactorial disease dependent on the influence of genetic and environmental factors. About 10% of cancers are associated with germline mutations, which predispose to a higher risk of developing cancer. Currently, the use of panels that identify susceptibility and/or association genes cancer has been increasingly used, both in clinical practice and in scientific research. Objective  To investigate genetic mutations in patients with a profile for hereditary cancer in individuals from a region of northeast Brazil, where there is a high frequency of endogenous and consanguineous marriages. Methods  A set of 17 genes ( BRCA1 , BRCA2 , APC , TP53 , PTEN , RET , VHL , RB1 , CDKN2 , CDH1 , CHEK2 , MLH1 , MSH2 , MSH6 , MUTYH , XPA , and XPC ) associated with cancer and hereditary syndromes were analyzed. Fifteen patients with a hereditary cancer profile were evaluated. Results  The pathogenic variant found was c.1187G > A (p.Gly396Asp), rs36053993 in the MUTYH gene in a male patient diagnosed with melanoma at the age of 43 years and a family history for this tumor. This gene encodes an important enzyme related to DNA repair and has been associated with other types of cancer, this is the first report of an association with melanoma, the biological plausibility of this association is given once the MUTYH protein is expressed in the skin tissue and is responsible for repairing damage caused, for example, by sun exposure. Conclusion  The results of this study suggest that this mutation may be important for the hereditary predisposition to melanoma, but a broader investigation of this mutation is needed.","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138622698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early is Better: Report of a Cowden Syndrome.","authors":"A Di Nora, G Pellino, A Di Mari, F Scarlata, F Greco, P Pavone","doi":"10.1055/s-0043-1777275","DOIUrl":"https://doi.org/10.1055/s-0043-1777275","url":null,"abstract":"<p><p>In the clinical practice, it is not common for pediatricians to visit children with overgrowth phenotype. When it happens, it is important to focus on the age of manifestations and research the pathogenic causes using appropriate genetic test. Cowden syndrome is one of these rare causes; it is an autosomal dominant genodermatosis characterized by multiple hamartomas of ectodermal, mesodermal, and endodermal origin. It is caused by loss of function mutations in the phosphatase and tensin homolog (PTEN) gene located on chromosome 10q23.1 Loss of function of the PTEN gene contributes to overgrowth and risk for a variety of cancers including breast, thyroid, endometrium, skin, kidneys, and colon. The early diagnosis of Cowden disease allows a careful monitoring of the patients who are facing the risk of cancer transformation, which is the principal complication of the condition.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetics and Genomics of Chronic Pancreatitis with a Focus on Disease Biology and Molecular Pathogenesis.","authors":"Erum Khan, Soura Chakrabarty, Sanobar Shariff, Mainak Bardhan","doi":"10.1055/s-0043-1776981","DOIUrl":"https://doi.org/10.1055/s-0043-1776981","url":null,"abstract":"<p><p>Chronic pancreatitis is a long-term fibroinflammatory condition of the pancreas with varying incidences across countries. The recent increase in its occurrence implies the involvement of genetic, hereditary, and unconventional risk factors. However, there is a lack of updated literature on recent advances in genetic polymorphisms of chronic pancreatitis. Therefore, this review aims to present recent findings on the genetic implications of chronic pancreatitis based on individual gene mechanisms and to discuss epigenetics and epistasis involved in the disease. Four mechanisms have been implicated in the pathogenesis of chronic pancreatitis, including premature activation of proteases, endoplasmic reticulum stress, ductal pathway dysfunction, and inflammatory pathway dysfunction. These mechanisms involve genes such as <i>PRSS1, PRSS2, SPINK, CEL, PNLIP, PNLIPRP2, CFTR, CaSR, CLDN2, Alpha 1 antitrypsin, and GGT1</i> . Studying genetic polymorphisms on the basis of altered genes and their products may aid clinicians in identifying predispositions in patients with and without common risk factors. Further research may also identify associations between genetic predispositions and disease staging or prognosis, leading to personalized treatment protocols and precision medicine.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10665123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe Hypernatremia as Presentation of Netherton Syndrome.","authors":"A Di Nora, M C Consentino, G Messina, T Timpanaro, P Smilari, P Pavone","doi":"10.1055/s-0043-1776983","DOIUrl":"https://doi.org/10.1055/s-0043-1776983","url":null,"abstract":"<p><p>Netherton syndrome is a rare, multisystem, autosomal recessive genodermatosis characterized by a triad of manifestations: congenital ichthyosis, immune dysregulation, and scalp anomalies. We report the case of a 1-month-old male infant evaluated for failure to thrive and feeding difficulties. At birth, the infant was admitted to intensive care for severe hypernatremia (natremia 186 mg/dL). Upon entering the ward, the general conditions were poor. He presented with diffuse erythrodermia. A dermatological evaluation showed evidence of \"invaginated trichuriasis,\" a typical sign of Netherton syndrome. Netherton syndrome is caused by a genetic mutation causing loss of function of the SPINK5 gene it encodes for the LEKTI protein, normally expressed in epithelia. Loss of LEKTI induces severe skin barrier defect. The history of the disease is characterized by serious potential complications in the first months of life, such as the risk of hypernatremic dehydration induced by high skin permeability, recurrent and/or severe infections, and growth retardation.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10665120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}