Pub Date : 2020-08-01DOI: 10.37421/1747-0862.2020.14.461
Klarskov Ck, Havelund Jf, Zegers Fd, Færgeman Nj, H. Schultz, F. Persson, B. Debrabant, Bjergaard Up, Kristensen Pl
Background: Glucocorticoid-induced diabetes mellitus (GIDM) is a serious side effect of glucocorticoid (GC) treatment that is associated with both increased mortality and morbidity, but not all patients develop GIDM when treated with GC. The reason is not known, and clinical risk factors predictive of type 2 diabetes do not predict GIDM. Previous metabolomics studies have found specific metabolic disturbances prior to clinical type 2 diabetes. This could also be true for GIDM. The primary aim of this study was to investigate whether distinct metabolic patterns in patients treated with high dose GC can predict development of GIDM. Material and Methods: Serum from 116 patients about to be treated with or in the first days of treatment with high-dose GC (>100 mg prednisolone equivalent) was analyzed with liquid chromatography-mass spectrometry (LC-MS) based nontargeted metabolomics. Clinical data were collected at baseline and through a 3-week follow-up period. 52 patients developed GIDM and 64 did not (control group). A logistic regression model and a predictive model was build and differences in the metabolome due to treatment with GC was tested in serum from patients without GC treatment (n=6) and patients with GC treatment (n=107). Results and Discussion: At univariate analysis three metabolites were associated with the development of GIDM. These metabolites could not be annotated to specific metabolites. A multi-metabolite approach could not predict GIDM, and this is different from previous findings in T2DM. This supports the hypothesis that the etiology of T2DM and GIDM is different. The biological significance of our finding remains unknown, but with the rapid development in the field of metabolomics and databases with increasing numbers of characterized metabolites, these metabolites may be identified. Conclusion: Our data indicate that the typical metabolic shifts in T2DM are not the same in GIDM. This supports the hypothesis that GIDM may have a pathophysiology different from T2DM. Furthermore, our data suggest that there is potential for identifying patients at risk of GIDM before clinical manifestation.
{"title":"Biomarkers for Development of Glucocorticoid-Induced Diabetes Mellitus - A Metabolomics-Based Prediction Model","authors":"Klarskov Ck, Havelund Jf, Zegers Fd, Færgeman Nj, H. Schultz, F. Persson, B. Debrabant, Bjergaard Up, Kristensen Pl","doi":"10.37421/1747-0862.2020.14.461","DOIUrl":"https://doi.org/10.37421/1747-0862.2020.14.461","url":null,"abstract":"Background: Glucocorticoid-induced diabetes mellitus (GIDM) is a serious side effect of glucocorticoid (GC) treatment that is associated with both increased mortality and morbidity, but not all patients develop GIDM when treated with GC. The reason is not known, and clinical risk factors predictive of type 2 diabetes do not predict GIDM. Previous metabolomics studies have found specific metabolic disturbances prior to clinical type 2 diabetes. This could also be true for GIDM. The primary aim of this study was to investigate whether distinct metabolic patterns in patients treated with high dose GC can predict development of GIDM. \u0000Material and Methods: Serum from 116 patients about to be treated with or in the first days of treatment with high-dose GC (>100 mg prednisolone equivalent) was analyzed with liquid chromatography-mass spectrometry (LC-MS) based nontargeted metabolomics. Clinical data were collected at baseline and through a 3-week follow-up period. 52 patients developed GIDM and 64 did not (control group). A logistic regression model and a predictive model was build and differences in the metabolome due to treatment with GC was tested in serum from patients without GC treatment (n=6) and patients with GC treatment (n=107). \u0000Results and Discussion: At univariate analysis three metabolites were associated with the development of GIDM. These metabolites could not be annotated to specific metabolites. A multi-metabolite approach could not predict GIDM, and this is different from previous findings in T2DM. This supports the hypothesis that the etiology of T2DM and GIDM is different. The biological significance of our finding remains unknown, but with the rapid development in the field of metabolomics and databases with increasing numbers of characterized metabolites, these metabolites may be identified. Conclusion: Our data indicate that the typical metabolic shifts in T2DM are not the same in GIDM. This supports the hypothesis that GIDM may have a pathophysiology different from T2DM. Furthermore, our data suggest that there is potential for identifying patients at risk of GIDM before clinical manifestation.","PeriodicalId":88269,"journal":{"name":"Journal of molecular and genetic medicine : an international journal of biomedical research","volume":"14 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44768179","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 : 2020-01-22DOI: 10.37421/1747-0862.2020.14.464
Benberin, T. Voshchenkova, G. Abildinova, A. Borovikova, A. Nagimtayeva
The increasing prevalence of type 2 diabetes (T2D) underlines the urgent need for proactive strategies to prevent and control T2D. A fairly large number of studies show that T2D is a complex metabolic disease caused by lifestyle, environment and genetic factors. Thus, the study of a genetic predisposition to diabetes is of great importance. At the same time, one of the most effective methods, besides genome-wide researches, is the use of polymorphic markers of various candidate genes, i.e., those genes, protein products of which (enzymes, regulatory proteins and peptides, structural proteins) can be potentially involved in the development of this disease. The study of genetic markers of type 2 diabetes association is relevant worldwide. The aim of this study was to search for genetic markers associated with the development of T2D in individuals of the Kazakh population.
{"title":"Analysis of Polymorphisms Associated with type 2 Diabetes in the Kazakh Population","authors":"Benberin, T. Voshchenkova, G. Abildinova, A. Borovikova, A. Nagimtayeva","doi":"10.37421/1747-0862.2020.14.464","DOIUrl":"https://doi.org/10.37421/1747-0862.2020.14.464","url":null,"abstract":"The increasing prevalence of type 2 diabetes (T2D) underlines the urgent need for proactive strategies to prevent and control T2D. A fairly large number of studies show that T2D is a complex metabolic disease caused by lifestyle, environment and genetic factors. Thus, the study of a genetic predisposition to diabetes is of great importance. At the same time, one of the most effective methods, besides genome-wide researches, is the use of polymorphic markers of various candidate genes, i.e., those genes, protein products of which (enzymes, regulatory proteins and peptides, structural proteins) can be potentially involved in the development of this disease. The study of genetic markers of type 2 diabetes association is relevant worldwide. The aim of this study was to search for genetic markers associated with the development of T2D in individuals of the Kazakh population.","PeriodicalId":88269,"journal":{"name":"Journal of molecular and genetic medicine : an international journal of biomedical research","volume":"14 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2020-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42451386","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 : 2020-01-01DOI: 10.37421/1747-0862.2020.14.S1
Erhan Yarar
This review discusses multiple aspects of Major Depressive Disease (MDD) and Brain Derived Neurotrophic Factor (BDNF) in terms of epigenetics, natural substances and translational medicine as treatment options for MDD. Diagnosis is still based upon psychiatrist’s education and experience and unfortunately there is still no test marker to diagnose patient’s mental health status. BDNF has a vital and complex role in diagnosing psychiatric conditions such as MDD. Conventional drugs and standard medical approachment to MDD come up short in increasing BDNF levels so the translational medicine might be a candidate to fortify the treatment and BDNF to be a reliable candidate for diagnosis and prognosis of MDD and other psychiatric conditions. It will be contextualized the exogenous components as capable as increasing the BDNF levels in MDD patients which is found usually low. Natural substance’s application as a tool of translational medicine will be screened as long as the limited data permits for the very reason that the translational medicine helps increase BDNF levels without causing side and adverse effects caused by standard medications. The need to revisit of natural compound’s neglected importance and their application in MDD will be articulated.
{"title":"Natural Substances and Botanicals as Modulators in Major Depressive Disease: Focus on BDNF - A Review","authors":"Erhan Yarar","doi":"10.37421/1747-0862.2020.14.S1","DOIUrl":"https://doi.org/10.37421/1747-0862.2020.14.S1","url":null,"abstract":"This review discusses multiple aspects of Major Depressive Disease (MDD) and Brain Derived Neurotrophic Factor (BDNF) in terms of epigenetics, natural substances and translational medicine as treatment options for MDD. Diagnosis is still based upon psychiatrist’s education and experience and unfortunately there is still no test marker to diagnose patient’s mental health status. BDNF has a vital and complex role in diagnosing psychiatric conditions such as MDD. Conventional drugs and standard medical approachment to MDD come up short in increasing BDNF levels so the translational medicine might be a candidate to fortify the treatment and BDNF to be a reliable candidate for diagnosis and prognosis of MDD and other psychiatric conditions. It will be contextualized the exogenous components as capable as increasing the BDNF levels in MDD patients which is found usually low. Natural substance’s application as a tool of translational medicine will be screened as long as the limited data permits for the very reason that the translational medicine helps increase BDNF levels without causing side and adverse effects caused by standard medications. The need to revisit of natural compound’s neglected importance and their application in MDD will be articulated.","PeriodicalId":88269,"journal":{"name":"Journal of molecular and genetic medicine : an international journal of biomedical research","volume":"14 1","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70041252","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 : 2020-01-01DOI: 10.37421/1747-0862.2020.14.462
S. El-Bisari, D. Alyounis, W. Sayed, S. Uppal
Introduction: Chromosomal mosaicism is characterized by the presence of more than one chromosomally different cell line in an individual. Preimplantation chromosomal mosaicism is characterized by the presence of a mixture of chromosomally different cell lines in an embryo. Studies show that mosaicism for whole chromosomes (aneuploidies) in one or more cells (blastomeres) occurred in more than 75% of cleavage stage embryos, whilst 3%-24% of blastocyst stage embryos are chromosomally mosaic. Aim: The purpose of this study was to standardize and validate a Next Generation Sequencing (NGS) method for comprehensive chromosome testing for aneuploidies and to study the level of mosaicism in cleavages stage vs. blastocyst stage embryos. Methods: The validation involved a retrospective blind assessment of whole genome amplification (WGA) products from 14 cleavages stage embryo biopsies (blastomeres), 6 blastocyst stage embryo biopsies (TE), in addition to their 20 discarded blastocyst stage whole embryos. 42.8% of the cleavages stage embryos showed mosaicism, whilst results between the trophectoderm (TE) biopsies (TEB) and their whole embryos at blastocyst stage showed total concordance as no mosaicism was observed. NGS sensitivity and specificity for calling aneuploidy was found to be 100%. Conclusion: This is the first study reporting preclinical validation and accuracy assessment of the Ion semiconductor sequencing technology in studying the level of mosaicism in cleavage stage and TE biopsies blastocyst stage embryos vs. their whole embryos. The high level of mosaicism in cleavages stage embryos compared to blastocyst stage embryos does not recommend the PGT-A to be performed on cleavage stage embryos. The NGS proved to be a robust methodology in clinical application of PGT-A.
{"title":"Chromosomal Mosaicism in Cleavage Stage Embryos vs. Blastocyst Stage Embryos","authors":"S. El-Bisari, D. Alyounis, W. Sayed, S. Uppal","doi":"10.37421/1747-0862.2020.14.462","DOIUrl":"https://doi.org/10.37421/1747-0862.2020.14.462","url":null,"abstract":"Introduction: Chromosomal mosaicism is characterized by the presence of more than one chromosomally different cell line in an individual. Preimplantation chromosomal mosaicism is characterized by the presence of a mixture of chromosomally different cell lines in an embryo. Studies show that mosaicism for whole chromosomes (aneuploidies) in one or more cells (blastomeres) occurred in more than 75% of cleavage stage embryos, whilst 3%-24% of blastocyst stage embryos are chromosomally mosaic. Aim: The purpose of this study was to standardize and validate a Next Generation Sequencing (NGS) method for comprehensive chromosome testing for aneuploidies and to study the level of mosaicism in cleavages stage vs. blastocyst stage embryos. Methods: The validation involved a retrospective blind assessment of whole genome amplification (WGA) products from 14 cleavages stage embryo biopsies (blastomeres), 6 blastocyst stage embryo biopsies (TE), in addition to their 20 discarded blastocyst stage whole embryos. 42.8% of the cleavages stage embryos showed mosaicism, whilst results between the trophectoderm (TE) biopsies (TEB) and their whole embryos at blastocyst stage showed total concordance as no mosaicism was observed. NGS sensitivity and specificity for calling aneuploidy was found to be 100%. Conclusion: This is the first study reporting preclinical validation and accuracy assessment of the Ion semiconductor sequencing technology in studying the level of mosaicism in cleavage stage and TE biopsies blastocyst stage embryos vs. their whole embryos. The high level of mosaicism in cleavages stage embryos compared to blastocyst stage embryos does not recommend the PGT-A to be performed on cleavage stage embryos. The NGS proved to be a robust methodology in clinical application of PGT-A.","PeriodicalId":88269,"journal":{"name":"Journal of molecular and genetic medicine : an international journal of biomedical research","volume":"14 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70041083","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 : 2020-01-01DOI: 10.37421/1747-0862.2020.14.466
L. Bergman, M. Schaffer, A. Livof, I. Ostfeld, N. Asna
Leptomeningeal dissemination (LM) is a major complication of a systemic cancer. In this paper, we will present a rare case of LM as the first presenting feature of an unknown primary. The patient had a good response to systemic corticosteroids for a week but, surprisingly, after investigation, the primary tumor was suspected to be a gastric tumor. Sadly, the patient died a few days later. In a literature search, it was hard to find similar cases, and the suggested protocols are very vague about LM from an unknown tumor. This case demonstrates that LM can be the first presentation of a systemic tumor, raising questions on treatment with corticosteroids.
{"title":"A Rare Case of Unknown Primary with First Presentation of Leptomeningeal Dissemination: Case Approach and Literature Review","authors":"L. Bergman, M. Schaffer, A. Livof, I. Ostfeld, N. Asna","doi":"10.37421/1747-0862.2020.14.466","DOIUrl":"https://doi.org/10.37421/1747-0862.2020.14.466","url":null,"abstract":"Leptomeningeal dissemination (LM) is a major complication of a systemic cancer. In this paper, we will present a rare case of LM as the first presenting feature of an unknown primary. The patient had a good response to systemic corticosteroids for a week but, surprisingly, after investigation, the primary tumor was suspected to be a gastric tumor. Sadly, the patient died a few days later. In a literature search, it was hard to find similar cases, and the suggested protocols are very vague about LM from an unknown tumor. This case demonstrates that LM can be the first presentation of a systemic tumor, raising questions on treatment with corticosteroids.","PeriodicalId":88269,"journal":{"name":"Journal of molecular and genetic medicine : an international journal of biomedical research","volume":"14 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70041486","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 : 2020-01-01DOI: 10.37421/JMGM.2020.14.446
J. Ziani, Z. Douhi, M. Bennani, S. Elloudi, H. Baybay, Mernissi Fz
Madame F, 55 years old with a story; four miscarriages and two fetal deaths in utero. At 40 years old, she had a brutal motor deficit in the left lower limb and then in the homolateral upper limb associated with left hemifacialparaesthesia with complete recovery 10 years ago.
{"title":"Sneddon Syndrome without Antiphospholipid Antibodies","authors":"J. Ziani, Z. Douhi, M. Bennani, S. Elloudi, H. Baybay, Mernissi Fz","doi":"10.37421/JMGM.2020.14.446","DOIUrl":"https://doi.org/10.37421/JMGM.2020.14.446","url":null,"abstract":"Madame F, 55 years old with a story; four miscarriages and two fetal deaths in utero. At 40 years old, she had a brutal motor deficit in the left lower limb and then in the homolateral upper limb associated with left hemifacialparaesthesia with complete recovery 10 years ago.","PeriodicalId":88269,"journal":{"name":"Journal of molecular and genetic medicine : an international journal of biomedical research","volume":"14 1","pages":"1-1"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70054346","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 : 2020-01-01DOI: 10.37421/JMGM.2020.14.447
Al-Buali Majed J, Al-Sunini Muna M, Al-Faraj Jaffer S, A. Ahmed A, Al-Mohammed Salah M, Zaal Hani R, Al- Mousa Haider H
Background: Perlman syndrome is an uncommon genetic disorder grouped with overgrowth syndrome in which an abnormal increase in the size of the body or a body part of the infant often noticed at birth. The disorder, usually affects the kidneys as main findings. Perlman syndrome inherited as an autosomal recessive pattern. People with this condition are generally born with renal abnormalities also called renal hamartomas, nephroblastomatosis also been grouped with Renal cell carcinoma. The characteristic features include polyhydramnios, fetal overgrowth, including macrocephaly, neonatal macrosomia, visceromegaly mainly hepatomegaly and nephromegaly, dysmorphic facial features, and an increased risk for Wilms’ tumor at an early age. The prognosis of Perlman syndrome is poor with high morbidity and mortality rate. Material and Methods: We report 3 months old female infant from Saudi origin product of consanguineous marriage with prenatal sonographic signs suggestive of Perlman Syndrome specifically polyhydramnios, bilateral nephromegaly with fetal ascites. The clinical course was marked by neonatal respiratory distress, cyanosis and refractory hypoxemia with chylothorax required mechanical ventilation. Frequent hospitalization since that due to frequent attacks of apnea and chest infections. Discussion and Conclusion: The constellation of clinical presentation and radiological finding confirmed by Molecular investigations showed a homozygous variant c.1810C>T p.(Gln604*) in the DIS3L2 gene (OMIM : 614184 ) which is consistent with Autosomal Recessive Perlman syndrome.
{"title":"Neonatal Nephromegaly Due to Homozygous Variant in the DIS3L2 Gene is Consistent with the Genetic Diagnosis of Perlman Syndrome","authors":"Al-Buali Majed J, Al-Sunini Muna M, Al-Faraj Jaffer S, A. Ahmed A, Al-Mohammed Salah M, Zaal Hani R, Al- Mousa Haider H","doi":"10.37421/JMGM.2020.14.447","DOIUrl":"https://doi.org/10.37421/JMGM.2020.14.447","url":null,"abstract":"Background: Perlman syndrome is an uncommon genetic disorder grouped with overgrowth syndrome in which an abnormal increase in the size of the body or a body part of the infant often noticed at birth. The disorder, usually affects the kidneys as main findings. Perlman syndrome inherited as an autosomal recessive pattern. People with this condition are generally born with renal abnormalities also called renal hamartomas, nephroblastomatosis also been grouped with Renal cell carcinoma. The characteristic features include polyhydramnios, fetal overgrowth, including macrocephaly, neonatal macrosomia, visceromegaly mainly hepatomegaly and nephromegaly, dysmorphic facial features, and an increased risk for Wilms’ tumor at an early age. The prognosis of Perlman syndrome is poor with high morbidity and mortality rate. Material and Methods: We report 3 months old female infant from Saudi origin product of consanguineous marriage with prenatal sonographic signs suggestive of Perlman Syndrome specifically polyhydramnios, bilateral nephromegaly with fetal ascites. The clinical course was marked by neonatal respiratory distress, cyanosis and refractory hypoxemia with chylothorax required mechanical ventilation. Frequent hospitalization since that due to frequent attacks of apnea and chest infections. Discussion and Conclusion: The constellation of clinical presentation and radiological finding confirmed by Molecular investigations showed a homozygous variant c.1810C>T p.(Gln604*) in the DIS3L2 gene (OMIM : 614184 ) which is consistent with Autosomal Recessive Perlman syndrome.","PeriodicalId":88269,"journal":{"name":"Journal of molecular and genetic medicine : an international journal of biomedical research","volume":"14 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70054394","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 : 2020-01-01DOI: 10.37421/JMGM.2020.14.443
N. Jaekel, M. Bauer, B Behre, Allam Hk
Introduction: Differential diagnosis of polyglobulia/erythrocytosis which is caused by deregulated erythropoiesis with an overproduction of red blood cells resulting in elevated hemoglobin and hematocrit levels is a diagnostic challenge. Case Report: A 31-year-old man was referred to us with a suspected diagnosis of polycythemia vera (a clonal myeloproliferative neoplasm) because of erythrocytosis. One year before, he suffered from an ischemic central retinal vein occlusion of unknown cause. Aspirin treatment was initiated. His mother was diagnosed with a JAK2V617F negative polycythemia vera years earlier and treated with phlebotomies as well as aspirin. Apart from erythrocytosis, laboratory analysis showed a normal white blood cell and platelet counts. The differential blood picture and lactate dehydrogenase were within the normal ranges. Molecular testing for BCR-ABL, JAK2V617F and Calreticulin gene mutations by PCR was negative. Bone marrow biopsy was normal without signs for a myeloproliferative neoplasm. As almost all patients with polycythemia vera carry the phenotype-driver mutation JAK2V617F, further genetic testing for congenital causes of erythrocytosis was conducted. Mutations in the EPO-receptor gene were not found, but a very rare heterozygous point mutation in the beta-globin-chain [exon 2 (c.119A>C) leading to a change in codon 40 (CAG>CCG)] was detected by next generation sequencing. This rare variant belongs to the high oxygen affinity hemoglobinopathies leading to a reduction of oxygen supply in tissues and an increase in red cell production. Conclusion: The diagnosis of a JAK2 mutation negative polycythemia vera must always be questioned and congenital causes of erythrocytosis excluded as the therapeutic and prognostic consequences are immense. Rare variants of hemoglobinopathies, particularly those with high oxygen affinity need to be excluded by molecular testing.
{"title":"A Rare Hemoglobinopathy as a Cause of Erythrocytosis in a Patient with Suspected JAK2V617F Negative Polycythemia Vera: A Case Report","authors":"N. Jaekel, M. Bauer, B Behre, Allam Hk","doi":"10.37421/JMGM.2020.14.443","DOIUrl":"https://doi.org/10.37421/JMGM.2020.14.443","url":null,"abstract":"Introduction: Differential diagnosis of polyglobulia/erythrocytosis which is caused by deregulated erythropoiesis with an overproduction of red blood cells resulting in elevated hemoglobin and hematocrit levels is a diagnostic challenge. Case Report: A 31-year-old man was referred to us with a suspected diagnosis of polycythemia vera (a clonal myeloproliferative neoplasm) because of erythrocytosis. One year before, he suffered from an ischemic central retinal vein occlusion of unknown cause. Aspirin treatment was initiated. His mother was diagnosed with a JAK2V617F negative polycythemia vera years earlier and treated with phlebotomies as well as aspirin. Apart from erythrocytosis, laboratory analysis showed a normal white blood cell and platelet counts. The differential blood picture and lactate dehydrogenase were within the normal ranges. Molecular testing for BCR-ABL, JAK2V617F and Calreticulin gene mutations by PCR was negative. Bone marrow biopsy was normal without signs for a myeloproliferative neoplasm. As almost all patients with polycythemia vera carry the phenotype-driver mutation JAK2V617F, further genetic testing for congenital causes of erythrocytosis was conducted. Mutations in the EPO-receptor gene were not found, but a very rare heterozygous point mutation in the beta-globin-chain [exon 2 (c.119A>C) leading to a change in codon 40 (CAG>CCG)] was detected by next generation sequencing. This rare variant belongs to the high oxygen affinity hemoglobinopathies leading to a reduction of oxygen supply in tissues and an increase in red cell production. Conclusion: The diagnosis of a JAK2 mutation negative polycythemia vera must always be questioned and congenital causes of erythrocytosis excluded as the therapeutic and prognostic consequences are immense. Rare variants of hemoglobinopathies, particularly those with high oxygen affinity need to be excluded by molecular testing.","PeriodicalId":88269,"journal":{"name":"Journal of molecular and genetic medicine : an international journal of biomedical research","volume":"14 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70054229","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 : 2020-01-01DOI: 10.37421/JMGM.2020.14.445
J. Ziani, Z. Douhi, M. Bennani, S. Elloudi, H. Baybay, Mernissi Fz
A 20-year-old woman with a history of contact with animals. She has had a rash for 2 years. Clinical examination revealed an eruption of non-follicular papules and micropustules from the trunk and upper limbs, on the scalp of alopecic plaques with floury dander and a sign of positive traction.
{"title":"An Unusual Presentation of Dermatophytid Reaction","authors":"J. Ziani, Z. Douhi, M. Bennani, S. Elloudi, H. Baybay, Mernissi Fz","doi":"10.37421/JMGM.2020.14.445","DOIUrl":"https://doi.org/10.37421/JMGM.2020.14.445","url":null,"abstract":"A 20-year-old woman with a history of contact with animals. She has had a rash for 2 years. Clinical examination revealed an eruption of non-follicular papules and micropustules from the trunk and upper limbs, on the scalp of alopecic plaques with floury dander and a sign of positive traction.","PeriodicalId":88269,"journal":{"name":"Journal of molecular and genetic medicine : an international journal of biomedical research","volume":"14 1","pages":"1-1"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70054279","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 : 2020-01-01DOI: 10.37421/JMGM.2020.14.455
Sarr Pd, Bailis Sa, S. Touré, Diop Jpd, Y. Dia, B. Mbengue, M. SyllaNiang, O. Faye, A. Dièye, R NdiayeDiallo
Background: The loss of function in TP53 gene is an early event of carcinogenesis and is now considered as a full etiological factor in oral squamous cell carcinoma (OSCC). The most common polymorphism in this gene that is associated to OSCC and has been extensively studied as a potential risk factor for the development of malignancies is the single nucleotide polymorphism (SNP) encoding either proline or arginine at residue 72. Today, despite the multiplicity of publications and approaches used, the contradiction of the results have not remove the ambiguity of the possible impact of this polymorphism in OSCC. So we aimed this meta-analysis to investigate the distribution of TP53 codon 72 genotypes and alleles in patients with OSCC and healthy matched controls, by using an ethnicity subgroups analysis. Method: A literature search was conducted to identify studies concerning TP53 codon 72 polymorphism and OSCC risk. Retrieved publications from 2000 to 2014 were classified by ethnicity, according to the sampling collection continent. Allelic frequencies were estimated by using genotypic data and Hardy-Weinberg Equilibrium and distributions were checked with Chi-2 test. Statistical tests for contrast models of association were performed with Proline allele as reference stratum. Results: Arg allele distribution was almost similar in both cases and controls for African and Caucasian populations whereas Arg frequency was significantly greater in cases than in controls for Asians (p=0.011). After stratified statistical analyses, we’ve found again a significant association between Arginine allele and OSCC risk in the Asian subgroup (OR=1.31; 95% CI=1.09-1.58; P=0.004). Conclusion: This current study revealed that allelic distribution of TP53 Arg72Pro polymorphism may depend on ethnicity and latitude, and highlighted that Arginine carrier in Asian populations may be considered to be predisposed to OSCC.
{"title":"Association of the TP53 Arg72Pro Polymorphism with Oral Squamous Cell Carcinoma: A Meta-Analysis","authors":"Sarr Pd, Bailis Sa, S. Touré, Diop Jpd, Y. Dia, B. Mbengue, M. SyllaNiang, O. Faye, A. Dièye, R NdiayeDiallo","doi":"10.37421/JMGM.2020.14.455","DOIUrl":"https://doi.org/10.37421/JMGM.2020.14.455","url":null,"abstract":"Background: The loss of function in TP53 gene is an early event of carcinogenesis and is now considered as a full etiological factor in oral squamous cell carcinoma (OSCC). The most common polymorphism in this gene that is associated to OSCC and has been extensively studied as a potential risk factor for the development of malignancies is the single nucleotide polymorphism (SNP) encoding either proline or arginine at residue 72. Today, despite the multiplicity of publications and approaches used, the contradiction of the results have not remove the ambiguity of the possible impact of this polymorphism in OSCC. So we aimed this meta-analysis to investigate the distribution of TP53 codon 72 genotypes and alleles in patients with OSCC and healthy matched controls, by using an ethnicity subgroups analysis. Method: A literature search was conducted to identify studies concerning TP53 codon 72 polymorphism and OSCC risk. Retrieved publications from 2000 to 2014 were classified by ethnicity, according to the sampling collection continent. Allelic frequencies were estimated by using genotypic data and Hardy-Weinberg Equilibrium and distributions were checked with Chi-2 test. Statistical tests for contrast models of association were performed with Proline allele as reference stratum. Results: Arg allele distribution was almost similar in both cases and controls for African and Caucasian populations whereas Arg frequency was significantly greater in cases than in controls for Asians (p=0.011). After stratified statistical analyses, we’ve found again a significant association between Arginine allele and OSCC risk in the Asian subgroup (OR=1.31; 95% CI=1.09-1.58; P=0.004). Conclusion: This current study revealed that allelic distribution of TP53 Arg72Pro polymorphism may depend on ethnicity and latitude, and highlighted that Arginine carrier in Asian populations may be considered to be predisposed to OSCC.","PeriodicalId":88269,"journal":{"name":"Journal of molecular and genetic medicine : an international journal of biomedical research","volume":"14 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70054537","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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