Global Medical Genetics最新文献

{"title":"Molecular Evaluation of Joubert Syndrome and Hearing Impairment in a Patient with Ataxic Cerebral Palsy.","authors":"N Sreedevi,&nbsp;N Swapna,&nbsp;Santosh Maruthy,&nbsp;T Jayakumar,&nbsp;Charles Sylvester","doi":"10.1055/s-0043-1771184","DOIUrl":"https://doi.org/10.1055/s-0043-1771184","url":null,"abstract":"<p><p>Joubert syndrome (JBTS) is a rare autosomal recessive or X-linked congenital brain malformation with strong genetic heterogeneity. Other neurological features of JBTS include hypotonia, ataxia, developmental delay, and cognitive impairment. Hearing loss with JBTS has been reported in the literature. We present the case of a 3.5-year-old boy born to a healthy consanguineous South Indian couple who was presented with ataxic cerebral palsy (CP) and hearing impairment; medical reports confirmed typical brain malformations of JBTS. Hearing impairment was screened by audiological assessment, which confirmed the presence of severe-profound hearing loss with outer hair cell dysfunction. Whole-exome sequencing (WES) was performed to know the molecular aspects of the condition and to detect any novel mutations. The homozygous mutation <i>AHI1</i> c.2023G > A associated with JBTS type 3 and <i>GJB2</i> c.71G > A mutation associated with hearing impairment were identified. Sanger sequencing was performed to validate the result and it identified heterozygous <i>AHI1</i> c.2023G > A and <i>GJB2</i> c.71G > A in the patient's parents. This study confirms the diagnosis of JBTS by WES helps identify the genetic causes of hereditary disorders that accelerate genetic evaluation and counseling for at-risk families.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 3","pages":"190-193"},"PeriodicalIF":1.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10370468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9941495","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":"Identification of Plasma Thrombopoietin Level and Its Significance in Patients with Aplastic Anemia and Myelodysplastic Syndrome.","authors":"Mengying Zhang, Gaochao Zhang, Fangfang Xu, Mengyuan Liu, Xifeng Dong, Weiwei Qi, Huaquan Wang","doi":"10.1055/s-0043-1771456","DOIUrl":"10.1055/s-0043-1771456","url":null,"abstract":"<p><p><b>Objective</b>  Our objective was to investigate the concentration of plasma thrombopoietin (TPO) in patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS), as well as its relationship with patients' responses to recombined human TPO (rhTPO) therapy. <b>Methods</b>  We detected the concentration of plasma TPO in 31 patients with AA, 27 patients with MDS, and 11 normal controls using enzyme-linked immunosorbent assay. <b>Results</b>  The median concentration of plasma TPO in patients with AA, MDS, and controls was (841.08 ± 768.64), (212.41 ± 338.93), and (35.09 ± 18.21) pg/mL, respectively. The TPO concentration in patients with AA and MDS was significantly higher than that in controls ( <i>p</i>  < 0.05). The median platelet (PLT) counts were (184 ± 34) ×10 ⁹ /L in the control group and (24 ± 19) ×10 ⁹ /L and (80 ± 71) ×10 ⁹ /L in AA and MDS patients, respectively. Negative correlations were found between plasma TPO concentration and PLT counts as well as megakaryocytes in bone marrow ( <i>p</i>  < 0.05). In AA patients treated with rhTPO, a negative correlation was observed between increased PLT counts and pretreatment TPO levels ( <i>p</i>  < 0.05). <b>Conclusion</b>  Plasma TPO concentration in AA and MDS was significantly higher than that in normal controls. Plasma TPO was negatively correlated with peripheral blood PLT counts and bone marrow megakaryocyte counts. The pretreatment TPO level may serve as a prognostic indicator for the therapeutic effect of rhTPO in AA patients.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 3","pages":"194-198"},"PeriodicalIF":1.5,"publicationDate":"2023-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10411100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9970187","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":"Role of Molecular Targeted Therapeutic Drugs in Treatment of Glioblastoma: A Review Article.","authors":"Himanshu Singh","doi":"10.1055/s-0043-57028","DOIUrl":"https://doi.org/10.1055/s-0043-57028","url":null,"abstract":"Abstract Glioblastoma is remarkably periodic primary brain tumor, characterizing an eminently heterogeneous pattern of neoplasms that are utmost destructive and threatening cancers. An enhanced and upgraded knowledge of the various molecular pathways that cause malignant changes in glioblastoma has resulted in advancement of numerous biomarkers and the interpretation of various agents that pointedly target tumor cells and microenvironment. In this review, literature or information on various targeted therapy for glioblastoma is discussed. English language articles were scrutinized in plentiful directory or databases like PubMed, ScienceDirect, Web of Sciences, Google Scholar, and Scopus. The important keywords used for searching databases are “Glioblastoma,” “Targeted therapy in glioblastoma,” “Therapeutic drugs in glioblastoma,” and “Molecular targets in glioblastoma.”","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 2","pages":"42-47"},"PeriodicalIF":1.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10110362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9383913","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":"Enabling Real-World Data to Accelerate the Development of Innovative Cancer Biomarkers.","authors":"Chen Yeh","doi":"10.1055/s-0043-1768993","DOIUrl":"https://doi.org/10.1055/s-0043-1768993","url":null,"abstract":"<p><p>The molecular diagnostics industry has historically relied on sanitized clinical trials and commoditized data sources to inform its biomarker discovery and validation process-an under-substantiated approach that was ultra-expensive, resource-consuming and did not reflect how representative a new biomarker would be in broader patient populations. In an effort to gain more accurate insight into the patient experience and bring innovative biomarkers to market more efficiently and accurately, the industry is now expanding into extended real-world data. To access the needed breadth and depth of patient-centric data, diagnostic companies must collaborate with a healthcare data analytics partner that has three key assets: (i) a broad and deep megadata with metadata, (ii) a data-rich provider network, and (iii) an outcomes-improvement engine to support the next generation of molecular diagnostics (Dx) and therapeutics (Rx) development.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 2","pages":"97-100"},"PeriodicalIF":1.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9526500","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":"Association of Interleukin-1 Receptor Antagonist ( <i>IL-1RA</i> ) Gene Polymorphism with Community-Acquired Pneumonia in North Indian Children: A Case-Control Study.","authors":"Neha Verma,&nbsp;Shally Awasthi,&nbsp;Anuj K Pandey,&nbsp;Prashant Gupta","doi":"10.1055/s-0043-1770056","DOIUrl":"https://doi.org/10.1055/s-0043-1770056","url":null,"abstract":"<p><p><b>Background</b>  Community-acquired pneumonia (CAP) is the leading cause of death in children < 5 years of age. The primary objective of the study was to assess the association of <i>IL-1RA</i> gene polymorphism in children aged 2 to 59 months with CAP and the secondary objective was to assess the association of gene polymorphism with mortality among hospitalized CAP cases. <b>Study Design</b>  This case-control study was conducted in a tertiary teaching institute in Northern India. Hospitalized children aged 2 to 59 months with World Health Organization-defined CAP were included as cases after parental consent. Age-matched healthy controls were recruited from the immunization clinic of the hospital. Genotyping was done using polymerase chain reaction to analyze the variable number of tandem repeats of <i>IL-1RA</i> gene polymorphism. <b>Result</b>  From October 2019 to October 2021, 330 cases (123, 37.27% female), and 330 controls (151, 45.75% female) were recruited. Genotype A2/A2 of the <i>IL-1RA</i> gene was found to be associated with the increased risk for CAP children with adjusted odds ratio (AOR) of 12.24 (95% confidence interval [CI] 5.21-28.7, <i>p</i>  < 0.001). A2 and A4 alleles were also found to be at risk for CAP. A1/A2 genotype was found to be protective for CAP with an AOR of 0.29 (95% CI 0.19-19.0.45). The genotype A2/A2 and A2 allele of <i>IL-1RA</i> gene was associated with child mortality with CAP cases. <b>Conclusion</b>  In <i>IL1RA</i> gene, A2/A2 genotype and A2 allele were associated with increased risk of CAP and A1/A2 were found to be protective for CAP. The genotype A2/A2 and A2 was associated with CAP mortality.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 2","pages":"109-116"},"PeriodicalIF":1.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10275672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9716287","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":"Exposure to SARS-CoV-2 and Infantile Diseases.","authors":"Darja Kanduc","doi":"10.1055/s-0043-1768699","DOIUrl":"https://doi.org/10.1055/s-0043-1768699","url":null,"abstract":"<p><p><b>Background and Aim</b>  Immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in newborns and children after prophylactic immunization is currently a relevant research topic. The present study analyzes the issue by examining the possibility that the anti-SARS-CoV-2 immune responses are not uniquely directed against the virus but can-via molecular mimicry and the consequent cross-reactivity-also hit human proteins involved in infantile diseases. <b>Methods</b>  Human proteins that-if altered-associate with infantile disorders were searched for minimal immune pentapeptide determinants shared with SARS-CoV-2 spike glycoprotein (gp). Then, the shared pentapeptides were analyzed for immunologic potential and immunologic imprinting phenomena. <b>Results</b>  Comparative sequence analysis shows that: (1) numerous pentapeptides (namely, 54) are common to SARS-CoV-2 spike gp and human proteins that, when altered, are linked to infantile diseases; (2) all the shared peptides have an immunologic potential since they are present in experimentally validated SARS-CoV-2 spike gp-derived epitopes; and (3) many of the shared peptides are also hosted in infectious pathogens to which children can have already been exposed, thus making immunologic imprint phenomena feasible. <b>Conclusion</b>  Molecular mimicry and the consequent cross-reactivity can represent the mechanism that connects exposure to SARS-CoV-2 and various pediatric diseases, with a fundamental role of the immunologic memory and the history of the child's infections in determining and specifying the immune response and the pathologic autoimmune sequela.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 2","pages":"72-78"},"PeriodicalIF":1.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9408199","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":"NGS-Panel Diagnosis Developed for the Differential Diagnosis of Idiopathic Toe Walking and Its Application for the Investigation of Possible Genetic Causes for the Gait Anomaly.","authors":"David Pomarino,&nbsp;Anna Emelina,&nbsp;Jens Heidrich,&nbsp;Kevin Rostásy,&nbsp;Svenja Schirmer,&nbsp;Jan O Schönfeldt,&nbsp;Anneke Thren,&nbsp;Ferdinand Wagner,&nbsp;Johanna Ronja Thren,&nbsp;Nina Berger","doi":"10.1055/s-0043-57230","DOIUrl":"https://doi.org/10.1055/s-0043-57230","url":null,"abstract":"<p><p>Idiopathic toe walking (ITW) describes a condition affecting approximately 4.5% of children. Toe walking is an accompanying symptom for many hereditary disorders. This retrospective study uses next-generation sequencing-panel-diagnosis to investigate the feasibility of genetic testing to research the possible genetic causes of ITW and for differential diagnosis. Data were taken from our inhouse database, the minimum age for participants was 3 years. Underlying neurological or orthopaedic conditions were tested for and ruled out prior to diagnosing ITW. Patients, who experienced complications before, during or immediately after birth, children with autism, and patients toe walking less than 50% of the time were excluded. Eighty-nine patients were included in the study, in which 66 (74.2%) patients were boys and 23 (25.8%) girls. Mean age at testing was 7.7 years (range: 3-17 years). Fifteen of the 89 patients included in the study (16.9%) had a genetic variant identified as likely pathogenic or pathogenic by the genetics laboratory. Additionally, we found 129 variants of uncertain significance. About 65.2% of patients showed a pes cavus foot deformity, 27% of patients reportedly had at least one relative who also displayed the gait anomaly, and 37.1% had problems with their speech development. Despite the limitations of the sample size and the scope of our genetic testing targets, our results indicate that research into the genetic causes of ITW could better our understanding of the causes of ITW in otherwise healthy children, to help develop novel methods to detect serious conditions early. ITW could be an early onset symptom for further hereditary conditions.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 2","pages":"63-71"},"PeriodicalIF":1.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9389463","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":"Efficacy and Safety Analysis of Combination Therapy Consisting of Intravenous Immunoglobulin and Corticosteroids versus Respective Monotherapies in the Treatment of Relapsed ITP in Adults.","authors":"Lijun Fang,&nbsp;Jing Sun,&nbsp;Yongqiang Zhao,&nbsp;Ming Hou,&nbsp;Depei Wu,&nbsp;Yunfei Chen,&nbsp;Renchi Yang,&nbsp;Lei Zhang","doi":"10.1055/s-0043-1769087","DOIUrl":"https://doi.org/10.1055/s-0043-1769087","url":null,"abstract":"<p><p><b>Objective</b>  In this study, we aimed to evaluate the efficacy and safety of combination therapy, consisting of intravenous immunoglobulin (IVIg) and corticosteroids, in comparison to respective monotherapies in the treatment of relapsed immune thrombocytopenia (ITP) in adults. <b>Methods</b>  A retrospective analysis of clinical data was conducted on 205 adult patients with relapsed ITP who received first-line combination therapy or monotherapy in multiple centers across China from January 2010 to December 2022. The study evaluated the patients' clinical characteristics, efficacy, and safety. <b>Results</b>  We found that the proportion of patients with platelet counts in complete response was significantly higher in the combination group (71.83%) compared with the IVIg group (43.48%) and the corticosteroids group (23.08%). The mean PLT _max in the combination group (178 × 10 ⁹ /L) was significantly higher than that in the IVIg group (109 × 10 ⁹ /L) and the corticosteroids group (76 × 10 ⁹ /L). Additionally, the average time for platelet counts to reach 30 × 10 ⁹ /L, 50 × 10 ⁹ /L, and 100 × 10 ⁹ /L in the combination group was significantly shorter than in the monotherapy groups. The proportion curves for reaching these platelet counts during treatment were also significantly different from those in the monotherapy groups. However, there were no significant differences in the effective rate, clinical characteristics, and adverse events among the three groups. <b>Conclusion</b>  We concluded that combining IVIg and corticosteroids was a more effective and faster treatment for relapsed ITP in adults than using either therapy alone. The findings of this study provided clinical evidence and reference for the use of first-line combination therapy in the treatment of relapsed ITP in adults.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 2","pages":"87-96"},"PeriodicalIF":1.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9526501","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":"Role of Molecular Targeted Therapeutic Drugs in Treatment of Breast Cancer: A Review Article.","authors":"Himanshu Singh","doi":"10.1055/s-0043-57247","DOIUrl":"https://doi.org/10.1055/s-0043-57247","url":null,"abstract":"<p><p>Breast cancer is a multifactor, multistage, and heterogeneous disease. Systemic treatment of breast cancer has changed significantly over the last decade. With a better knowledge of the pathogenesis, researchers and scientists have discovered numerous signaling pathways and synonymous therapeutic targets in breast cancer. Because of the molecular nature of breast cancer, which makes it difficult to understand, previous attempts to treat or prevent it have failed. However, recent decades have provided effective therapeutic targets for treatment. In this review, literature or information on various targeted therapy for breast cancer is discussed. English language articles were explored in numerous directory or databases like PubMed, Web of Sciences, Google Scholar, ScienceDirect, and Scopus. The important keywords used for searching databases are \"Breast cancer,\" \"Targeted therapy in breast cancer,\" \"Therapeutic drugs in breast cancer,\" and \"Molecular targets in breast cancer.\"</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 2","pages":"79-86"},"PeriodicalIF":1.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9526507","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":"Molecular Screening for Urothelial Cancer: How Close We Are?","authors":"Athanasios Michas,&nbsp;Basileios Michas,&nbsp;Anastasios Tsitsibis,&nbsp;Nikolaos Tsoukalas","doi":"10.1055/s-0043-1768958","DOIUrl":"https://doi.org/10.1055/s-0043-1768958","url":null,"abstract":"<p><p>Early detection of urothelial cancer offers the potential for effective and successful treatment. Despite previous efforts, currently, there is not a well-validated, recommended screening program in any country. This integrative, literature-based review provides details on how recent molecular advances may further advance early tumor detection. The minimally invasive liquid biopsy is capable of identifying tumor material in human fluid samples from asymptomatic individuals. Circulating tumor biomarkers (cfDNA, exosomes, etc.) are very promising and are attracting the interest of numerous studies for the diagnosis of early-stage cancer. However, this approach definitely needs to be refined before clinical implementation. Nevertheless, despite the variety of current obstacles that require further research, the prospect of identifying urothelial carcinoma by a single urine or blood test seems truly intriguing.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 2","pages":"101-104"},"PeriodicalIF":1.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9526504","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}