Pub Date : 2022-06-13eCollection Date: 2022-06-01DOI: 10.1055/s-0042-1743260
Darja Kanduc
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.
{"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":"9 1","pages":"182-184"},"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}
Background Chronic myelomonocytic leukemia (CMML) is a myeloid neoplasm with features of the myelodysplastic syndromes (MDSs) and myeloproliferative neoplasm presenting with peripheral blood monocytosis and an inherent risk for transformation to acute myeloid leukemia, while the abnormal DNA methylation plays a critical role in the pathogenesis of MDS, which is a disease of disordered differentiation. Recently, with the rapid development of molecular biology, hypomethylating agents (HMAs) for the treatment of MDS has gradually become a research focus. The objective of this study was to evaluate the benefits and risks of HMAs for patients with CMML. Materials and Methods PubMed, Embase, the Cochrane Library, and three Chinese databases were searched for studies published before November 2020 that used HMAs in CMML. Results The pooled objective response rate (ORR), complete response (CR), and partial response (PR) were 50.0, 21.0, and 2.0%, respectively. The proportion of patients with minor response (MR) was significantly higher for decitabine (DAC) than for azacitidine (AZA). There was no significant difference in hematologic improvement, ORR, CR, and PR rates between the DAC and AZA groups. Hematological toxicity included neutropenia grade 3/4 (14.0%), anemia grade 3/4 (17.0%), and thrombocytopenia grade 3/4 (22.0%). Conclusion This study showed that HMAs were effective and safe in the treatment of CMML, but large multicenter study would be needed to confirm the efficacy of HMAs for the treatment of CMML with different risk level and genetic abnormality, to support individualization treatment theoretically.
{"title":"Efficacy and Safety of Hypomethylating Agents in Chronic Myelomonocytic Leukemia: A Single-Arm Meta-analysis","authors":"Xinhui Zheng, L. Lv, Xiangjun Li, E. Jiang","doi":"10.1055/s-0042-1744157","DOIUrl":"https://doi.org/10.1055/s-0042-1744157","url":null,"abstract":"Background Chronic myelomonocytic leukemia (CMML) is a myeloid neoplasm with features of the myelodysplastic syndromes (MDSs) and myeloproliferative neoplasm presenting with peripheral blood monocytosis and an inherent risk for transformation to acute myeloid leukemia, while the abnormal DNA methylation plays a critical role in the pathogenesis of MDS, which is a disease of disordered differentiation. Recently, with the rapid development of molecular biology, hypomethylating agents (HMAs) for the treatment of MDS has gradually become a research focus. The objective of this study was to evaluate the benefits and risks of HMAs for patients with CMML. Materials and Methods PubMed, Embase, the Cochrane Library, and three Chinese databases were searched for studies published before November 2020 that used HMAs in CMML. Results The pooled objective response rate (ORR), complete response (CR), and partial response (PR) were 50.0, 21.0, and 2.0%, respectively. The proportion of patients with minor response (MR) was significantly higher for decitabine (DAC) than for azacitidine (AZA). There was no significant difference in hematologic improvement, ORR, CR, and PR rates between the DAC and AZA groups. Hematological toxicity included neutropenia grade 3/4 (14.0%), anemia grade 3/4 (17.0%), and thrombocytopenia grade 3/4 (22.0%). Conclusion This study showed that HMAs were effective and safe in the treatment of CMML, but large multicenter study would be needed to confirm the efficacy of HMAs for the treatment of CMML with different risk level and genetic abnormality, to support individualization treatment theoretically.","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"9 1","pages":"141 - 151"},"PeriodicalIF":1.7,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44119402","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}
S. Kenanoglu, Nefise Kandemir, H. Akalın, Nuriye Gokce, Mehmet F. Gol, M. Gultekin, E. Koseoglu, Meral Mirza, M. Dundar
Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by a devastating decline in cognitive activities among all types of dementia, and it severely affects the quality of life. Late-onset AD (LOAD) occurs after the age of 65 years and develops sporadically. Although aging comes first along the main risk factors underlying LOAD, disease-causing susceptibility genes have been associated with disease pathogenesis. In our study, we included the genes PARP1 , POLB , HTRA2 , SLC1A2 , HS1BP3 , and DRD3 to be investigated in LOAD patients based on their expression levels. Within this framework, we aimed to determine the possible functions of these genes in the pathophysiology of the disease. We investigated whether the utilization of these genes as biomarkers in the early diagnosis of LOAD may help the treatment scheme to be applied in the clinic. We involved 50 individuals in the study and collected peripheral blood samples from the patients and control groups for molecular genetic analysis. Subsequently, RNA was extracted from the peripheral blood samples, and expression analyzes were performed using qualitative reverse transcription polymerase chain reaction. The results obtained were evaluated by using proper statistical methods. Our results demonstrated that there was no difference between patient and control groups in terms of HTRA2 , DRD3 , HS1BP3 , and POLB genes. The expression levels of the SLC1A2 and PARP1 genes were significantly lower in the patient group compared with the control group. In conclusion, we presume that the PARP1 and SLC1A2 genes can be utilized as molecular biomarkers for LOAD.
{"title":"Evaluation of Utilizing the Distinct Genes as Predictive Biomarkers in Late-Onset Alzheimer's Disease","authors":"S. Kenanoglu, Nefise Kandemir, H. Akalın, Nuriye Gokce, Mehmet F. Gol, M. Gultekin, E. Koseoglu, Meral Mirza, M. Dundar","doi":"10.1055/s-0042-1743570","DOIUrl":"https://doi.org/10.1055/s-0042-1743570","url":null,"abstract":"Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by a devastating decline in cognitive activities among all types of dementia, and it severely affects the quality of life. Late-onset AD (LOAD) occurs after the age of 65 years and develops sporadically. Although aging comes first along the main risk factors underlying LOAD, disease-causing susceptibility genes have been associated with disease pathogenesis. In our study, we included the genes PARP1 , POLB , HTRA2 , SLC1A2 , HS1BP3 , and DRD3 to be investigated in LOAD patients based on their expression levels. Within this framework, we aimed to determine the possible functions of these genes in the pathophysiology of the disease. We investigated whether the utilization of these genes as biomarkers in the early diagnosis of LOAD may help the treatment scheme to be applied in the clinic. We involved 50 individuals in the study and collected peripheral blood samples from the patients and control groups for molecular genetic analysis. Subsequently, RNA was extracted from the peripheral blood samples, and expression analyzes were performed using qualitative reverse transcription polymerase chain reaction. The results obtained were evaluated by using proper statistical methods. Our results demonstrated that there was no difference between patient and control groups in terms of HTRA2 , DRD3 , HS1BP3 , and POLB genes. The expression levels of the SLC1A2 and PARP1 genes were significantly lower in the patient group compared with the control group. In conclusion, we presume that the PARP1 and SLC1A2 genes can be utilized as molecular biomarkers for LOAD.","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"9 1","pages":"110 - 117"},"PeriodicalIF":1.7,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44226685","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}
Statement of Problem Prosthodontic planning in patients with temporomandibular joint disorders (TMDs) is a challenge for the clinicians. Purpose A differential biomarker identification could aid in developing methods for early detection and confirmation of TMD from other related conditions. Materials and Methods The present study identified candidate genes with possible association with TMDs. The observational study delineates genes from three datasets retrieved from DisGeNET database. The convergence of datasets identifies potential genes related to TMDs with associated complication such as osteoarthritis. Gene ontology analysis was also performed to identify the potential pathways associated with the genes belonging to each of the datasets. Results The preliminary analysis revealed vascular endothelial growth factor A ( VEGFA ), interleukin 1 β ( IL1B , and estrogen receptor 1 ( ESR1 ) as the common genes associated with all three phenotypes assessed. The gene ontology analysis revealed functional pathways in which the genes of each dataset were clustered. The chemokine and cytokine signaling pathway, gonadotropin-releasing hormone receptor pathway, cholecystokinin receptors (CCKR) signaling, and tumor growth factor (TGF)-β signaling pathway were the pathways most commonly associated with the phenotypes. The genes CCL2, IL6 , and IL1B were found to be the common genes across temporomandibular joint (TMJ) and TMJ + osteoarthritis (TMJ-OA) datasets. Conclusion Analysis through computational approach has revealed IL1B as the crucial candidate gene which could have a strong association with bone disorders. Nevertheless, several immunological pathways have also identified numerous genes showing putative association with TMJ and other related diseases. These genes have to be further validated using experimental approaches to acquire clarity on the mechanisms related to the pathogenesis.
{"title":"A Computational Data Mining Strategy to Identify the Common Genetic Markers of Temporomandibular Joint Disorders and Osteoarthritis","authors":"V. Jayaseelan, P. Arumugam","doi":"10.1055/s-0042-1743571","DOIUrl":"https://doi.org/10.1055/s-0042-1743571","url":null,"abstract":"Statement of Problem Prosthodontic planning in patients with temporomandibular joint disorders (TMDs) is a challenge for the clinicians. Purpose A differential biomarker identification could aid in developing methods for early detection and confirmation of TMD from other related conditions. Materials and Methods The present study identified candidate genes with possible association with TMDs. The observational study delineates genes from three datasets retrieved from DisGeNET database. The convergence of datasets identifies potential genes related to TMDs with associated complication such as osteoarthritis. Gene ontology analysis was also performed to identify the potential pathways associated with the genes belonging to each of the datasets. Results The preliminary analysis revealed vascular endothelial growth factor A ( VEGFA ), interleukin 1 β ( IL1B , and estrogen receptor 1 ( ESR1 ) as the common genes associated with all three phenotypes assessed. The gene ontology analysis revealed functional pathways in which the genes of each dataset were clustered. The chemokine and cytokine signaling pathway, gonadotropin-releasing hormone receptor pathway, cholecystokinin receptors (CCKR) signaling, and tumor growth factor (TGF)-β signaling pathway were the pathways most commonly associated with the phenotypes. The genes CCL2, IL6 , and IL1B were found to be the common genes across temporomandibular joint (TMJ) and TMJ + osteoarthritis (TMJ-OA) datasets. Conclusion Analysis through computational approach has revealed IL1B as the crucial candidate gene which could have a strong association with bone disorders. Nevertheless, several immunological pathways have also identified numerous genes showing putative association with TMJ and other related diseases. These genes have to be further validated using experimental approaches to acquire clarity on the mechanisms related to the pathogenesis.","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"9 1","pages":"159 - 165"},"PeriodicalIF":1.7,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46466690","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}
Xiaolei Xie, Hongyan Chai, Autumn Diadamo, Brittany Grommisch, J. Wen, Hui Z. Zhang, Peining Li
Background Cytogenomic analyses have been used to detect pathogenic copy number variants. Patients with deletions at 6q26-q27 present variable clinical features. We reported clinical and cytogenomic findings of eight unrelated patients with a deletion of 6q26-q27. A systematic review of the literature found 28 patients with a deletion of 6q26-q27 from 2010 to 2020. Results For these 36 patients, the sex ratio showed equal occurrence between males and females; 29 patients (81%) had a terminal deletion and seven patients (19%) had a proximal or distal interstitial deletion. Of the 22 patients with parental studies, deletions of de novo, maternal, paternal, and bi-parental inheritance accounted for 64, 18, 14, and 4% of patients, respectively. The most common clinical findings were brain abnormalities (100%) in fetuses observed by ultrasonography followed by developmental delay and intellectual disability (81%), brain abnormalities (72%), facial dysmorphism (66%), hypotonia (63%), learning difficulty or language delay (50%), and seizures (47%) in pediatric and adult patients. Anti-epilepsy treatment showed the effect on controlling seizures in these patients. Cytogenomic mapping defined one proximal critical region at 6q26 containing the putative haploinsufficient gene PRKN and one distal critical region at 6q27 containing two haploinsufficient genes DLL1 and TBP . Deletions involving the PRKN gene could associate with early-onset Parkinson disease and autism spectrum disorder; deletions involving the DLL1 gene correlate with the 6q terminal deletion syndrome. Conclusion The genotype–phenotype correlations for putative haploinsufficient genes in deletions of 6q26-q27 provided evidence for precise diagnostic interpretation, genetic counseling, and clinical management of patients with a deletion of 6q26-q27.
{"title":"Genotype–Phenotype Correlations for Putative Haploinsufficient Genes in Deletions of 6q26-q27: Report of Eight Patients and Review of Literature","authors":"Xiaolei Xie, Hongyan Chai, Autumn Diadamo, Brittany Grommisch, J. Wen, Hui Z. Zhang, Peining Li","doi":"10.1055/s-0042-1743568","DOIUrl":"https://doi.org/10.1055/s-0042-1743568","url":null,"abstract":"Background Cytogenomic analyses have been used to detect pathogenic copy number variants. Patients with deletions at 6q26-q27 present variable clinical features. We reported clinical and cytogenomic findings of eight unrelated patients with a deletion of 6q26-q27. A systematic review of the literature found 28 patients with a deletion of 6q26-q27 from 2010 to 2020. Results For these 36 patients, the sex ratio showed equal occurrence between males and females; 29 patients (81%) had a terminal deletion and seven patients (19%) had a proximal or distal interstitial deletion. Of the 22 patients with parental studies, deletions of de novo, maternal, paternal, and bi-parental inheritance accounted for 64, 18, 14, and 4% of patients, respectively. The most common clinical findings were brain abnormalities (100%) in fetuses observed by ultrasonography followed by developmental delay and intellectual disability (81%), brain abnormalities (72%), facial dysmorphism (66%), hypotonia (63%), learning difficulty or language delay (50%), and seizures (47%) in pediatric and adult patients. Anti-epilepsy treatment showed the effect on controlling seizures in these patients. Cytogenomic mapping defined one proximal critical region at 6q26 containing the putative haploinsufficient gene PRKN and one distal critical region at 6q27 containing two haploinsufficient genes DLL1 and TBP . Deletions involving the PRKN gene could associate with early-onset Parkinson disease and autism spectrum disorder; deletions involving the DLL1 gene correlate with the 6q terminal deletion syndrome. Conclusion The genotype–phenotype correlations for putative haploinsufficient genes in deletions of 6q26-q27 provided evidence for precise diagnostic interpretation, genetic counseling, and clinical management of patients with a deletion of 6q26-q27.","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"9 1","pages":"166 - 174"},"PeriodicalIF":1.7,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47269304","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}
Background Dendritic cell (DC) tumor vaccine has been extensively utilized in preclinical and clinical studies; however, this technique has encountered many difficulties, particularly in late-stage tumor patients. For those, ex vivo-induced DCs are actuallymyeloid-derived suppressive cells-derived DCs (MDSC-DCs). MDSCs with immunosuppressive activity, but not monocytes, became the major DC precursor. Thus, how to enhance antitumor activity of MDSC-DCs is urgent need to address. Methods We utilized 4T1 and MC38 tumor-bearing both wildtype and CC chemokine ligand 5 −/− (CCL5 −/− ) mice as animal models. MDSC-DCs were induced from splenocytes of these mice by granulocyte macrophage–colony stimulating factor/interleukin-4 with or without all-trans-retinoic acid (ATRA) in vitro for 7 days, then incubated with tumor-cell-lysis to treat mouse models for total three doses. For human MDSC-DCs, peripheral bloods from colorectal cancer patients were induced in vitro as murine cells with or without T- lymphocytes depletion to get rid of CCL5. Results Flow cytometry analysis showed that MDSCs from CCL5 −/− mice could be induced into a new type of CD24 + MDSC-DCs in the presence of ATRA, which had more antitumor activity than control. Antibody blocking and adoptive transfer experiments demonstrated that downregulation of regulatory T cells (Tregs) mediated the inhibition of CD24 + MDSC-DCs on tumor growth. Mechanically, CD24 + MDSC-DCs inhibited Tregs' polarization by secreting cytokine or coactivators' expression. What's important, decreasing CCL5 protein levels by T- lymphocytes depletion during both murine and human MDSC-DCs in vitro induction could also acquire CD24 + MDSC-DCs. Conclusion Knockdown of CCL5 protein during MDSC-DCs culture might provide a promising method to acquire DC-based tumor vaccines with high antitumor activity.
{"title":"CD24 + MDSC-DCs Induced by CCL5-Deficiency Showed Improved Antitumor Activity as Tumor Vaccines","authors":"Lei Huang, Zequn Ding, Yan Zhang","doi":"10.1055/s-0042-1743569","DOIUrl":"https://doi.org/10.1055/s-0042-1743569","url":null,"abstract":"Background Dendritic cell (DC) tumor vaccine has been extensively utilized in preclinical and clinical studies; however, this technique has encountered many difficulties, particularly in late-stage tumor patients. For those, ex vivo-induced DCs are actuallymyeloid-derived suppressive cells-derived DCs (MDSC-DCs). MDSCs with immunosuppressive activity, but not monocytes, became the major DC precursor. Thus, how to enhance antitumor activity of MDSC-DCs is urgent need to address. Methods We utilized 4T1 and MC38 tumor-bearing both wildtype and CC chemokine ligand 5 −/− (CCL5 −/− ) mice as animal models. MDSC-DCs were induced from splenocytes of these mice by granulocyte macrophage–colony stimulating factor/interleukin-4 with or without all-trans-retinoic acid (ATRA) in vitro for 7 days, then incubated with tumor-cell-lysis to treat mouse models for total three doses. For human MDSC-DCs, peripheral bloods from colorectal cancer patients were induced in vitro as murine cells with or without T- lymphocytes depletion to get rid of CCL5. Results Flow cytometry analysis showed that MDSCs from CCL5 −/− mice could be induced into a new type of CD24 + MDSC-DCs in the presence of ATRA, which had more antitumor activity than control. Antibody blocking and adoptive transfer experiments demonstrated that downregulation of regulatory T cells (Tregs) mediated the inhibition of CD24 + MDSC-DCs on tumor growth. Mechanically, CD24 + MDSC-DCs inhibited Tregs' polarization by secreting cytokine or coactivators' expression. What's important, decreasing CCL5 protein levels by T- lymphocytes depletion during both murine and human MDSC-DCs in vitro induction could also acquire CD24 + MDSC-DCs. Conclusion Knockdown of CCL5 protein during MDSC-DCs culture might provide a promising method to acquire DC-based tumor vaccines with high antitumor activity.","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"9 1","pages":"97 - 109"},"PeriodicalIF":1.7,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44145803","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}
Pub Date : 2022-02-11eCollection Date: 2022-03-01DOI: 10.1055/s-0042-1742488
{"title":"Contributing Reviewers in 2021.","authors":"","doi":"10.1055/s-0042-1742488","DOIUrl":"https://doi.org/10.1055/s-0042-1742488","url":null,"abstract":"","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"9 1","pages":"i-iv"},"PeriodicalIF":1.7,"publicationDate":"2022-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8837402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39789351","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}
Smita Hegde, Rajat Hegde, S. Kulkarni, Kusal K. Das, P. Gai, R. Bulagouda
Objective The goal of this research was to investigate the gap junction beta 2 ( GJB2 ) gene mutations associated with nonsyndromic hearing loss individuals in North Karnataka, India. Materials and Methods For this study, patients with sensorineural genetic hearing abnormalities and a family history of deafness were included. A total of 35 patients from 20 families have been included in the study. The patient's DNA was isolated from peripheral blood samples. The GJB2 gene coding region was analyzed through Sanger sequencing. Results There is no changes in the first exon of the GJB2 gene. Nine different variants were recorded in second exon of the targeted gene. W24X and W77X are two nonsense mutations and three polymorphisms viz. R127H, V153I, and I33T were reported along with four 3′-UTR variants. A total (9/20) of 45% of families have been identified with mutations in the targeted gene. Conclusion GJB2 mutations were identified in 19 deaf-mute patients (19/35), and 13 patients were homozygous for the mutations identified in our study cohort. In our study, W24X mutation was found to be the pathogenic with a high percentage, prompting further evaluation of the other genes, along with the study of additional genetic or external causes in the families, which is essential.
{"title":"Analysis of Genetic Variations in Connexin 26 ( GJB2 ) Gene among Nonsyndromic Hearing Impairment: Familial Study","authors":"Smita Hegde, Rajat Hegde, S. Kulkarni, Kusal K. Das, P. Gai, R. Bulagouda","doi":"10.1055/s-0042-1743257","DOIUrl":"https://doi.org/10.1055/s-0042-1743257","url":null,"abstract":"Objective The goal of this research was to investigate the gap junction beta 2 ( GJB2 ) gene mutations associated with nonsyndromic hearing loss individuals in North Karnataka, India. Materials and Methods For this study, patients with sensorineural genetic hearing abnormalities and a family history of deafness were included. A total of 35 patients from 20 families have been included in the study. The patient's DNA was isolated from peripheral blood samples. The GJB2 gene coding region was analyzed through Sanger sequencing. Results There is no changes in the first exon of the GJB2 gene. Nine different variants were recorded in second exon of the targeted gene. W24X and W77X are two nonsense mutations and three polymorphisms viz. R127H, V153I, and I33T were reported along with four 3′-UTR variants. A total (9/20) of 45% of families have been identified with mutations in the targeted gene. Conclusion GJB2 mutations were identified in 19 deaf-mute patients (19/35), and 13 patients were homozygous for the mutations identified in our study cohort. In our study, W24X mutation was found to be the pathogenic with a high percentage, prompting further evaluation of the other genes, along with the study of additional genetic or external causes in the families, which is essential.","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"9 1","pages":"152 - 158"},"PeriodicalIF":1.7,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47045387","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}
Pushpendra D. Pratap, Syed Tasleem Raza, Ghazala Zaidi, Shipra Kunwar, Sharique Ahmad, M. Charles, A. Eba, Muneshwar Rajput
Objectives Cervical cancer (CC) is one of the most destructive disease caused by persistent HPV infection which affects women worldwide, especially in developing countries. The genetic basis of host immune response especially cytokine function has been shown to influence CC susceptibility. Studies have demonstrated that IL-10 gene polymorphism have been associated with numerous malignancies, but in context to CC results were inconclusive. Though, aim of our study to investigate the association between IL-10 -1082A/G and -819C/T promoter polymorphism and CC susceptibility. Material and Methods This study comprised 192 women with CC and 200 controls. HPV detection was done by RT-PCR and genotyping was assessed through PCR-RFLP method. Serum concentration of IL-10 measured by ELISA. Results Women with AG and AG+GG genotypes of IL-10 -1082A/G had two-fold increased risk of CC [OR, 2.35 (95% CI, 1.54–3.58), p = 0.005], [OR, 2.03 (95% CI, 1.36–3.04), p = 0.0005] compared to controls. Women with G allele of -1082A/G polymorphism had linked with CC susceptibility [OR, 1.39 (95% CI, 1.02–1.88), p = 0.036] compared to controls. No significant difference was found between patients and controls in the genotype or allele frequencies of IL–10 -819C/T polymorphism [OR, 1.00 (95% CI, 0.63–1.58), p = 0.99]. The level of serum concentration of IL-10 was significantly higher in cases compared to controls. Conclusion These findings help to understand that polymorphism of IL-10 -1082A/G gene is associated with increased risk of CC development and can serve as a marker of genetic susceptibility to CC.
{"title":"Genetic Variants in Interleukin-10 Gene Association with Susceptibility and Cervical Cancer Development: A Case Control Study","authors":"Pushpendra D. Pratap, Syed Tasleem Raza, Ghazala Zaidi, Shipra Kunwar, Sharique Ahmad, M. Charles, A. Eba, Muneshwar Rajput","doi":"10.1055/s-0042-1743262","DOIUrl":"https://doi.org/10.1055/s-0042-1743262","url":null,"abstract":"Objectives Cervical cancer (CC) is one of the most destructive disease caused by persistent HPV infection which affects women worldwide, especially in developing countries. The genetic basis of host immune response especially cytokine function has been shown to influence CC susceptibility. Studies have demonstrated that IL-10 gene polymorphism have been associated with numerous malignancies, but in context to CC results were inconclusive. Though, aim of our study to investigate the association between IL-10 -1082A/G and -819C/T promoter polymorphism and CC susceptibility. Material and Methods This study comprised 192 women with CC and 200 controls. HPV detection was done by RT-PCR and genotyping was assessed through PCR-RFLP method. Serum concentration of IL-10 measured by ELISA. Results Women with AG and AG+GG genotypes of IL-10 -1082A/G had two-fold increased risk of CC [OR, 2.35 (95% CI, 1.54–3.58), p = 0.005], [OR, 2.03 (95% CI, 1.36–3.04), p = 0.0005] compared to controls. Women with G allele of -1082A/G polymorphism had linked with CC susceptibility [OR, 1.39 (95% CI, 1.02–1.88), p = 0.036] compared to controls. No significant difference was found between patients and controls in the genotype or allele frequencies of IL–10 -819C/T polymorphism [OR, 1.00 (95% CI, 0.63–1.58), p = 0.99]. The level of serum concentration of IL-10 was significantly higher in cases compared to controls. Conclusion These findings help to understand that polymorphism of IL-10 -1082A/G gene is associated with increased risk of CC development and can serve as a marker of genetic susceptibility to CC.","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"9 1","pages":"129 - 140"},"PeriodicalIF":1.7,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48406665","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}
Mannose-binding lectin 2 (MBL2) is a serine protease which is believed to be an important factor in the inherited immune system. In this article, we present a coronavirus disease 2019 (COVID-19) family of five patients: a 56-year-old father, a 51-year-old mother, two sons aged 23 and 21 years, and a 15-year-old daughter. According to the results of MBL2 rs1800450 variant analysis performed, the father had homozygous mutant, the mother had homozygous normal, and the three children had heterozygous mutant genotype. When we compared the clinical parameters and genotypes, MBL2 gene polymorphism plays a very important role in COVID-19 susceptibility and severe disease. The family, which makes up our study, is the proof of this situation, and it contains important implications for host factors and COVID-19.
{"title":"Mannose-Binding Lectin 2 Gene Polymorphism during Pandemic: COVID-19 Family","authors":"T. Tukek, S. Pehlivan, Y. Oyacı, U. Işoğlu-Alkaç","doi":"10.1055/s-0042-1743258","DOIUrl":"https://doi.org/10.1055/s-0042-1743258","url":null,"abstract":"Mannose-binding lectin 2 (MBL2) is a serine protease which is believed to be an important factor in the inherited immune system. In this article, we present a coronavirus disease 2019 (COVID-19) family of five patients: a 56-year-old father, a 51-year-old mother, two sons aged 23 and 21 years, and a 15-year-old daughter. According to the results of MBL2 rs1800450 variant analysis performed, the father had homozygous mutant, the mother had homozygous normal, and the three children had heterozygous mutant genotype. When we compared the clinical parameters and genotypes, MBL2 gene polymorphism plays a very important role in COVID-19 susceptibility and severe disease. The family, which makes up our study, is the proof of this situation, and it contains important implications for host factors and COVID-19.","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"9 1","pages":"185 - 188"},"PeriodicalIF":1.7,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45406306","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}
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