Global Medical Genetics最新文献

{"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}

{"title":"The Frequency of <i>SMN1, SMN2</i> Copy Numbers in 246 Turkish Cases Analyzed with MLPA Method.","authors":"Sinem Yalcintepe,&nbsp;Yasemin Karal,&nbsp;Selma Demir,&nbsp;Emine Ikbal Atli,&nbsp;Engin Atli,&nbsp;Damla Eker,&nbsp;Cisem Mail,&nbsp;Drenushe Zhuri,&nbsp;Hazal Sezginer Guler,&nbsp;Hakan Gurkan","doi":"10.1055/s-0043-1770055","DOIUrl":"https://doi.org/10.1055/s-0043-1770055","url":null,"abstract":"<p><p>This study aimed to define the copy numbers of <i>SMN1</i> and <i>SMN2</i> genes and the diagnosis rate and carrier frequency of spinal muscular atrophy (SMA) in the Thrace region of Turkey. In this study, the frequency of deletions in exons 7 and 8 in the <i>SMN1</i> gene and <i>SMN2</i> copy numbers were investigated. A total of 133 cases with the preliminary diagnosis of SMA and 113 cases with the suspicion of being an SMA carrier from independent families were analyzed by multiplex ligation-dependent probe amplification method for <i>SMN1</i> and <i>SMN2</i> gene copy numbers. <i>SMN1</i> homozygous deletions were detected in 34 patients (25.5%) of 133 cases with the suspicion of SMA. Cases diagnosed with SMA type I was 41.17% (14/34), 29.4% (10/34) with type II, 26.4% (9/34) with type III, and 2.94% (1/34) with type IV. The SMA carrier rate was 46.01% in 113 cases. In 34 SMA cases, <i>SMN2</i> copy numbers were: two copies - 28 cases (82.3%), three copies - 6 cases (17.6%). <i>SMN2</i> homozygous deletions were detected in 15% (17/113) of carrier analysis cases. The consanguinity rate of the parents was 23.5% in SMA diagnosed cases. In this study, we had a 25.5% of SMA diagnosis rate and 46% SMA carrier frequency. The current study also showed the relatively low consanguinity rate of the Thrace region, with 23.5% according to the east of Turkey.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 2","pages":"117-122"},"PeriodicalIF":1.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10275673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9716286","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":"The Role of the <i>Matrix Metalloproteinase-9</i> Gene in Tumor Development and Metastasis: A Narrative Review.","authors":"Datis Kalali","doi":"10.1055/s-0043-1768166","DOIUrl":"https://doi.org/10.1055/s-0043-1768166","url":null,"abstract":"<p><p>Matrix metalloproteinase-9 (MMP-9) is one of the widely studied enzymes of the extracellular matrix which can degrade various matrix biomolecules. The gene coding for this enzyme has been found to be associated with various multifactorial diseases, including cancer. More specifically, the expression of MMP-9 and polymorphisms of its gene have been found to be correlated with the formation and the invasiveness of different types of cancer. Hence, the latter gene can potentially be used both as a clinical genetic marker and a possible target in anticancer therapy. The present minireview explores the role of the <i>MMP-9</i> gene in the process of tumor formation, growth, and metastasis and presents an overview of the polymorphisms of the gene associated with cancer as well as its regulation mechanisms, to provide an insight into the potential clinical applications. Nevertheless, further clinical trials and research are still required to reach more valuable conclusions for the clinical implications of the recent findings.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 2","pages":"48-53"},"PeriodicalIF":1.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10110361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9383912","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 Gene Mutations in Acute Myeloid Leukemia: A Review Article.","authors":"Himanshu Singh,&nbsp;Magesh Kumar,&nbsp;Himanshu Kanungo","doi":"10.1055/s-0043-1770768","DOIUrl":"https://doi.org/10.1055/s-0043-1770768","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is an immensely heterogeneous disease characterized by the clonal growth of promyelocytes or myeloblasts in bone marrow as well as in peripheral blood or tissue. Enhancement in the knowledge of the molecular biology of cancer and recognition of intermittent mutations in AML contribute to favorable circumstances to establish targeted therapies and enhance the clinical outcome. There is high interest in the development of therapies that target definitive abnormalities in AML while eradicating leukemia-initiating cells. In recent years, there has been a better knowledge of the molecular abnormalities that lead to the progression of AML, and the application of new methods in molecular biology techniques has increased that facilitating the advancement of investigational drugs. In this review, literature or information on various gene mutations for AML is discussed. English language articles were scrutinized in plentiful directories or databases like PubMed, Science Direct, Web of Sciences, Google Scholar, and Scopus. The important keywords used for searching databases is \"Acute myeloid leukemia\", \"Gene mutation in Acute myeloid leukemia\", \"Genetic alteration in Acute myeloid leukemia,\" and \"Genetic abnormalities in Acute myeloid leukemia.\"</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 2","pages":"123-128"},"PeriodicalIF":1.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10289861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9717733","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":"<i>PMM2</i> -CDG T237M Mutation in a Patient with Cerebral Palsy-Like Phenotypes Reported from South India.","authors":"N Sreedevi,&nbsp;N Swapna,&nbsp;Santosh Maruthy,&nbsp;H S Meghavathi,&nbsp;Charles Sylvester","doi":"10.1055/s-0043-1769494","DOIUrl":"https://doi.org/10.1055/s-0043-1769494","url":null,"abstract":"<p><p>Congenital disorder of glycosylation (CDG) is an autosomal recessively inherited disorder. Hypotonia, stroke-like episodes, and peripheral neuropathy are also associated with the condition that typically develops during infancy. The patient, a 12-year-old girl born to healthy consanguineous parents, was diagnosed with cerebral palsy as a child. The affected patient has hypotonia, inadequate speech, strabismus, and developmental delay with mild mental retardation, which are key symptoms of CDG. Whole-exome sequencing (WES) identified the known missense pathogenic variant <i>PMM2</i> c.710 C > T, p.T237M in the patient coding for the phosphomannomutase 2 (PMM2) confirming molecular testing of CDG. The patient's parents carried heterozygous <i>PMM2</i> c.710 C > T variants. This study highlights the importance of WES in patients with a developmental disability or other neurological conditions, which is also useful in screening risk factors in couples with infertility or miscarriage issues.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 2","pages":"105-108"},"PeriodicalIF":1.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10234699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9578376","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":"Replication Timing Aberration of <i>KIF14</i> and <i>MDM4</i> / <b><i>PI3KC</i></b> 2 <i>β</i> Alleles and Aneuploidy as Markers of Chromosomal Instability and Poor Treatment Response in Ewing Family Tumor Patients.","authors":"Fernanda Rocha Rojas Ayala,&nbsp;Jeffrey William Martin,&nbsp;Carmen Silvia Bertuzzo","doi":"10.1055/s-0043-1768238","DOIUrl":"https://doi.org/10.1055/s-0043-1768238","url":null,"abstract":"<p><p>Replication timing of allelic gene pairs is strictly regulated according to expression, genome stability, and epigenetic changes, and tumorigenesis may be associated with changes in the allelic replication in various tumors. Our aim was to determine whether such alterations had a prognostic value in Ewing's family tumor (EFT) patients. The <i>KIF14</i> and <i>MDM4</i> / <b><i>PI3KC</i></b> 2β and the centromeric satellite sequence of chromosomes 8 and 12 were used for replication timing assessments. Aneuploidy was assessed by enumerating the copy numbers of chromosomes 8 and 12. Replication timing and aneuploidy were detected cytogenetically using multicolors fluorescence in situ hybridization assay applied in 135 EFT. Patients with trisomy 8 presented an association with an asynchronous replication pattern (SD) of <i>MDM4</i> / <b><i>PI3KC</i></b> 2β genes ( <i>p</i>  = 0.013). Trisomy 12 was associated with a synchronous pattern (DD) of <i>KIF14</i> probe signals ( <i>p</i>  = 0.04). The DD synchronous replication pattern of <i>KIF14</i> showed a correlation with age ( <i>p</i>  < 0.0001), and the SS synchronous replication pattern of the same locus showed a correlation with lung metastatic ( <i>p</i>  = 0.012). The subgroup of patients presenting with multiplet signals of <i>MDM4</i> / <b><i>PI3KC</i></b> 2β showed an association with treatment response ( <i>p</i>  = 0.045) and age ( <i>p</i>  = 0.033). Replication pattern of <i>KIF14</i> may, significantly, be associated with chromosomal instability as <i>MDM4</i> / <b><i>PI3KC</i></b> 2β may be a considerably new marker of poor treatment response in EFT patients.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 2","pages":"54-62"},"PeriodicalIF":1.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9444901","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}