Global Medical Genetics最新文献

{"title":"Dihydropyridine Reductase Deficiency: Acute Encephalopathy Related to Folinic Acid Treatment Interruption in a Girl.","authors":"Maria Grazia Pappalardo,&nbsp;Alessandra Di Nora,&nbsp;Andrea Giugno,&nbsp;Concetta Meli,&nbsp;Annamaria Sapuppo,&nbsp;Piero Pavone,&nbsp;Agata Fiumara","doi":"10.1055/s-0042-1756661","DOIUrl":"https://doi.org/10.1055/s-0042-1756661","url":null,"abstract":"<p><p>We reported the case of acute encephalopathy related to colonic acid treatment interruption in a 12-year-old female child presenting to our unit with episodes of vomiting, headache, irritability, acute confusional state, seizures, and left lower limb hypotonia. Brain magnetic resonance imaging (MRI) showed signs of vasogenic and cytotoxic edema at the cerebellar level bilaterally, and lesions at the temporo-occipito-parietal right level, temporomandibular left, and right thalamic with swelling of the convolutions and reduced differentiation between white and gray matter. The patient had suspended the folinic acid treatment at least 6 months before the present admission. The relation between the clinical signs presented by the girl and folic acid deficiency was confirmed by the result of laboratory assessment and by the answer to the notable clinical improvement with the renewal of folinic acid treatment. Dihydropteridine reductase (DHPR) deficiency is a rare autosomal recessive genetic disorder caused by the quinoid dihydropteridine reductase (QDPR) gene mutations. DHPR deficiency impairs the synthesis of the tetrahydrobiopterin (BH4), an essential cofactor for the hydroxylation of the aromatic amino acids phenylalanine, tyrosine, and tryptophan. When not precociously treated, the disorder may present whit severe neurologic impairment including developmental delay/intellective disability (DD/ID), microcephaly, seizures, movement disorders, cerebral palsy, and other neurological impairments. The clinical and neuroradiologic anomalies observed in our case were unusual, with signs previously unreported in patients with folic acid deficiency. The present case shows that the clinical presentation and MRI anomalies of the cerebral folic acid deficiency may be various and unusual compared with those reported in the literature, and it confirms the usefulness of the continuation of folinic acid treatment during the course of the disorder in patients with DHPR deficiency.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33468014","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 Oral Squamous Cell Carcinoma: Development and Current Strategies-A Review Article.","authors":"Himanshu Singh,&nbsp;Vedant Patel","doi":"10.1055/s-0042-1756663","DOIUrl":"https://doi.org/10.1055/s-0042-1756663","url":null,"abstract":"<p><p>Because of active advancement in the field of biomedicine, people have in-depth knowledge of biological nature of malignant tumors and are able to recognized the overexpression of different molecules such as vascular endothelial growth factor receptor, cyclin-dependent kinase, and programmed cell death receptor. Presently, various targeted therapeutic drugs are used in different clinical trials in those patients suffering from oral squamous cell carcinoma. In this review, we converse about the various targeted therapeutic drugs and their advancement in the treatment of oral squamous cell carcinoma. This review scrutinizes the existing documentation in the literature related to the targeted therapies for oral squamous cell carcinoma. English language articles were searched in various databases such as PubMed, Scopus, Science Direct, and Google Scholar. The keywords used for searching are \"oral squamous cell carcinoma,\" \"targeted therapy,\" and \"therapeutic drugs.\"</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33468013","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 Codon Usage, tRNA Availability, and Cell Proliferation in EBV Latency and (Re)Activation.","authors":"Darja Kanduc","doi":"10.1055/s-0042-1751301","DOIUrl":"https://doi.org/10.1055/s-0042-1751301","url":null,"abstract":"<p><p>Epstein-Barr nuclear antigen 1 (EBNA1) protein synthesis is inhibited during Epstein-Barr virus (EBV) latency and is resumed in EBV (re)activation. In analyzing the molecular mechanisms underpinning the translation of <i>EBNA1</i> in the human host, this article deals with two orders of data. First, it shows that the heavily biased codon usage of the <i>EBNA1</i> open reading frame cannot be translated due to its noncompliance with the human codon usage pattern and the corresponding tRNA pool. The <i>EBNA1</i> codon bias resides in the sequence composed exclusively of glycine and alanine, i.e., the Gly-Ala repeat (GAR). Removal of the nucleotide sequence coding for GAR results in an <i>EBNA1</i> codon usage pattern with a lower codon bias, thus conferring translatability to EBNA1. Second, the data bring cell proliferation to the fore as a conditio sine qua non for qualitatively and quantitatively modifying the host's tRNA pool as required by the translational needs of EBNA1, thus enabling viral reactivation. Taken together, the present work provides a biochemical mechanism for the pathogen's shift from latency to (re)activation and confirms the role of human codon usage as a first-line tool of innate immunity in inhibiting pathogens' expression. Immunologically, this study cautions against using codon optimization and proliferation-inducing substances such as glucocorticoids and adjuvants, which can (re)activate the otherwise quiescent, asymptomatic, and innocuous EBV infection. Lastly, the data pose the question whether the causal pathogenic role attributed to EBV should instead be ascribed to the carcinogenesis-associated cellular proliferation.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9477563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40367198","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":"Investigation on the Effects of Modifying Genes on the Spinal Muscular Atrophy Phenotype.","authors":"Drenushe Zhuri,&nbsp;Hakan Gurkan,&nbsp;Damla Eker,&nbsp;Yasemin Karal,&nbsp;Sinem Yalcintepe,&nbsp;Engin Atli,&nbsp;Selma Demir,&nbsp;Emine Ikbal Atli","doi":"10.1055/s-0042-1751302","DOIUrl":"https://doi.org/10.1055/s-0042-1751302","url":null,"abstract":"<p><p><b>Introduction</b>  Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by the degeneration of motor neurons, muscle weakness, and atrophy that leads to infant's death. The duplication of exon 7/8 in the <i>SMN2</i> gene reduces the clinical severity of disease, and it is defined as modifying effect. In this study, we aim to investigate the expression of modifying genes related to the prognosis of SMA like <i>PLS3</i> , <i>PFN2</i> , <i>ZPR1</i> , <i>CORO1C</i> , <i>GTF2H2</i> , <i>NRN1</i> , <i>SERF1A</i> , <i>NCALD</i> , <i>NAIP</i> , and <i>TIA1.</i> <b>Methods</b>  Seventeen patients, who came to Trakya University, Faculty of Medicine, Medical Genetics Department, with a preliminary diagnosis of SMA disease, and eight healthy controls were included in this study after multiplex ligation-dependent probe amplification analysis. Gene expression levels were determined by real-time reverse transcription polymerase chain reaction and delta-delta CT method by the isolation of RNA from peripheral blood of patients and controls. <b>Results</b>   <i>SERF1A</i> and <i>NAIP</i> genes compared between A group and B + C + D groups, and A group of healthy controls, showed statistically significant differences ( <i>p</i>  = 0.037, <i>p</i>  = 0.001). <b>Discussion</b>   <i>PLS3, NAIP</i> , and <i>NRN1</i> gene expressions related to SMA disease have been reported before in the literature. In our study, the expression levels of <i>SERF1A</i> , <i>GTF2H2</i> , <i>NCALD</i> , <i>ZPR1</i> , <i>TIA1</i> , <i>PFN2</i> , and <i>CORO1C</i> genes have been studied for the first time in SMA patients.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9444347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33447804","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":"A Narrative Review on Fanconi Anemia: Genetic and Diagnostic Considerations.","authors":"Preksha Sharma,&nbsp;Neha Sharma,&nbsp;Dhruva Sharma","doi":"10.1055/s-0042-1751303","DOIUrl":"https://doi.org/10.1055/s-0042-1751303","url":null,"abstract":"<p><p>Fanconi anemia (FA) is an autosomal recessive disorder, both genetically and phenotypically. It is characterized by chromosomal instability, progressive bone marrow failure, susceptibility to cancer, and various other congenital abnormalities. It involves all the three cell lines of blood. So far, biallelic mutations in 21 genes and one x-linked gene have been detected and found to be associated with FA phenotype. Signs and symptoms start setting in by the age of 4 to 7 years, mainly hematological symptoms. This includes pancytopenia, that is, a reduction in the number of white blood cells (WBCs), red blood cells (RBCs), and platelets. Therefore, the main criteria for diagnosis of FA include skeletal malformations, pancytopenia, hyperpigmentation, short stature, urogenital abnormalities, central nervous system, auditory, renal, ocular, and familial occurrence. Patients showing signs and symptoms of FA should be thoroughly evaluated. A complete blood count will reveal a reduced number of RBC, WBC, and platelets, that is, pancytopenia. Chromosomal breakage study/stress cytogenetics should be done in patients with severe pancytopenia. Momentousness timely diagnosis of current disease, prenatal diagnosis, and genetic counseling should be emphasized.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9444348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33447805","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":"A New 12q21 Deletion Syndrome: A Case Report and Literature Review.","authors":"Alessandra Di Nora,&nbsp;Greta De Costa,&nbsp;Alessia Di Mari,&nbsp;Marco Montemagno,&nbsp;Vito Pavone,&nbsp;Piero Pavone","doi":"10.1055/s-0042-1748171","DOIUrl":"https://doi.org/10.1055/s-0042-1748171","url":null,"abstract":"<p><p>Diagnosis in children with physical and intellective anomalies is very challenging because of the wide spectrum of causes. Array-based comparative genomic hybridization (CGH) has acquired an important role in pediatric diagnostic work up. Interstitial deletion of the long arm of chromosome 12 are rare. To date, deletions including the 12q21 region were reported in only 13 patients. The main features are development delay, eyes and central nervous system anomalies, and heart and kidney defects. We describe a 3-year-old boy with a de novo 15 Mb deletion at 12q21.1q21.32, never reported in the last cases. By screening the critical region and reviewing the literature, we identified SYT1, PPP1R12A, and CEP290 such as pathogenetic genes.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40549814","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":"Investigating the Genetic Etiology of Pediatric Patients with Peripheral Hypotonia Using the Next-Generation Sequencing Method.","authors":"Damla Eker,&nbsp;Hakan Gurkan,&nbsp;Yasemin Karal,&nbsp;Sinem Yalcintepe,&nbsp;Selma Demir,&nbsp;Engin Atli,&nbsp;Serap T Karasalihoglu","doi":"10.1055/s-0042-1745873","DOIUrl":"https://doi.org/10.1055/s-0042-1745873","url":null,"abstract":"<p><p><b>Background</b>  Hypotonia occurs as a result of neurological dysfunction in the brain, brainstem, spinal cord, motor neurons, anterior horn cells, peripheral nerves, and muscles. Although the genotype-phenotype correlation can be established in 15 to 30% of patients, it is difficult to obtain a correlation in most cases. <b>Aims</b>  This study was aimed to investigate the genetic etiology in cases of peripheral hypotonia that could not be diagnosed using conventional methods. <b>Methods</b>  A total of 18 pediatric patients with peripheral hypotonia were included. They were referred to our genetic disorders diagnosis center from the Pediatric Neurology Department with a prediagnosis of hypotonia. A custom designed multigene panel, including <i>ACTA1</i> , <i>CCDC78</i> , <i>DYNC1H1</i> , <i>GARS</i> , <i>RYR1</i> , <i>COL6A1</i> , <i>COL6A2</i> , <i>COL6A3</i> , <i>FKRP</i> , <i>FKTN</i> , <i>IGHMBP2</i> , <i>LMNA</i> , <i>LAMA2</i> , <i>LARGE1</i> , <i>MTM1</i> , <i>NEM</i> , <i>POMGnT1</i> , <i>POMT1</i> , <i>POMT2</i> , and <i>SEPN1</i> , was used for genetic analysis using next-generation sequencing (NGS). <b>Results</b>  In our study, we found 13 variants including pathogenic (two variants in LAMA2) and likely pathogenic variants (three variants in RYR1 and POMGnT1) and variants of uncertain clinical significance (eight variants in RYR1, COL6A3, COL6A2, POMGnT1 and POMT1) in 11 (61%) out of 18 patients. In one of our patients, a homozygous, likely pathogenic c.1649G > A, p.(Ser550Asn) variant was defined in the <i>POMGnT1</i> gene which was associated with a muscle-eye-brain disease phenotype. <b>Conclusion</b>  The contribution of an in-house designed gene panel in the etiology of peripheral hypotonia with a clinical diagnosis was 5.5%. An important contribution with the clinical diagnosis can be made using the targeted multigene panels in larger samples.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9286875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40602248","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 <i>PAX7</i> Gene rs766325 and rs4920520 Polymorphisms in the Etiology of Non-syndromic Cleft Lip and Palate: A Genetic Study.","authors":"Mahamad Irfanulla Khan,&nbsp;Prashanth Cs,&nbsp;Narasimhamurty Srinath","doi":"10.1055/s-0042-1748531","DOIUrl":"https://doi.org/10.1055/s-0042-1748531","url":null,"abstract":"<p><p>Non-syndromic cleft lip and palate (NSCLP) is one of the most common birth defects in humans with an overall prevalence of ∼1 in 700 live births around the world. The etiology of NSCLP is complex involving multiple genes, environmental factors, and gene-to-gene interactions. Several genome-wide associations (GWA) studies have shown the association of the paired box 7 ( <i>PAX7</i> ) gene in the etiology of cleft lip and palate in different populations worldwide. However, there are no reported studies on the association between the rs766325 and rs4920520 polymorphisms and the risk of developing NSCLP in the Indian population. Hence, the present study aimed to test for the probable association between rs766325 and rs4920520 polymorphisms among NSCLP Indian population using a case-parent trio design. Forty case-parent trios were selected from the cleft lip and palate center based on the inclusion and exclusion criteria. Genomic DNA was isolated from the cases and their parents. The rs766325 and rs4920520 polymorphisms of the <i>PAX7</i> gene were analyzed for their association using the MassARRAY analysis. The statistical analysis was done using the PLINK software. The rs766325 and rs4920520 polymorphisms were tested for the Hardy-Weinberg equilibrium. None of the polymorphisms showed any statistical significance. Hence, the rs766325 and rs4920520 polymorphisms of the <i>PAX7</i> gene were found to be not associated with NSCLP in the Indian case-parent trios.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9286873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40602246","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":"SARS-CoV-2-Induced Immunosuppression: A Molecular Mimicry Syndrome.","authors":"Darja Kanduc","doi":"10.1055/s-0042-1748170","DOIUrl":"https://doi.org/10.1055/s-0042-1748170","url":null,"abstract":"<p><p><b>Background</b>  Contrary to immunological expectations, decay of adaptive responses against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) characterizes recovered patients compared with patients who had a severe disease course or died following SARS-CoV-2 infection. This raises the question of the causes of the virus-induced immune immunosuppression. Searching for molecular link(s) between SARS-CoV-2 immunization and the decay of the adaptive immune responses, SARS-CoV-2 proteome was analyzed for molecular mimicry with human proteins related to immunodeficiency. The aim was to verify the possibility of cross-reactions capable of destroying the adaptive immune response triggered by SARS-CoV-2. <b>Materials and Methods</b>  Human immunodeficiency-related proteins were collected from UniProt database and analyzed for sharing of minimal immune determinants with the SARS-CoV-2 proteome. <b>Results</b>  Molecular mimicry and consequent potential cross-reactivity exist between SARS-CoV-2 proteome and human immunoregulatory proteins such as nuclear factor kappa B (NFKB), and variable diversity joining V(D)J recombination-activating gene (RAG). <b>Conclusion</b>  The data (1) support molecular mimicry and the associated potential cross-reactivity as a mechanism that can underlie self-reactivity against proteins involved in B- and T-cells activation/development, and (2) suggest that the extent of the immunosuppression is dictated by the extent of the immune responses themselves. The higher the titer of the immune responses triggered by SARS-CoV-2 immunization, the more severe can be the cross-reactions against the human immunodeficiency-related proteins, the more severe the immunosuppression. Hence, SARS-CoV-2-induced immunosuppression can be defined as a molecular mimicry syndrome. Clinically, the data imply that booster doses of SARS-CoV-2 vaccines may have opposite results to those expected.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40602247","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":"Nucleotide Sequence Sharing between the Human Genome and Primers for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Detection.","authors":"Darja Kanduc","doi":"10.1055/s-0042-1743260","DOIUrl":"10.1055/s-0042-1743260","url":null,"abstract":"<p><p>This study shows that oligonucleotide sequences are shared between the human genome and primers that have been proposed/used for SARS-CoV-2 detection by polymerase chain reaction (PCR). The high level of sharing (namely, up to 19mer with a maximum number of gaps equal to 2) might bear implications for the diagnostic validity of SARS-CoV-2 detection by PCR.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9192186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"57973964","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}