Blood Cells Molecules and Diseases最新文献

{"title":"Inherited disorders of hemoglobin: A review of old and new diagnostic methods","authors":"Emily Franco ,&nbsp;Kristine A. Karkoska ,&nbsp;Patrick T. McGann","doi":"10.1016/j.bcmd.2023.102758","DOIUrl":"10.1016/j.bcmd.2023.102758","url":null,"abstract":"<div><p><span>The genetic<span> regulation of hemoglobin is complex and there are a number of genetic abnormalities that result in clinically important hemoglobin disorders. Here, we review the molecular pathophysiology<span> of hemoglobin disorders and review both old and new methods of diagnosing these disorders. Timely diagnosis of hemoglobinopathies in infants is essential to coordinate optimal life-saving interventions, and accurate identification of carriers of deleterious mutations allows for </span></span></span>genetic counseling<span><span><span><span><span> and informed family planning. The initial laboratory workup of inherited disorders of hemoglobin should include a complete blood count (CBC) and peripheral </span>blood smear, followed by carefully selected tests based on clinical suspicion and available methodology. We discuss the utility and limitations of the various methodologies to fractionate hemoglobin, including </span>cellulose acetate and citrate agar </span>hemoglobin electrophoresis<span>, isoelectric focusing<span>, high-resolution high-performance liquid chromatography, and capillary zone electrophoresis<span>. Recognizing that most of the global burden of hemoglobin disorders exists in low- and middle-income countries, we review the increasingly available array of point-of-care-tests (POCT), which have an increasingly important role in expanding early diagnosis programs to address the global burden of sickle cell disease, including Sickle SCAN, HemoTypeSC, Gazelle </span></span></span></span>Hb Variant<span>, and Smart LifeLC. A comprehensive understanding of the molecular pathophysiology of hemoglobin and the globin genes<span>, as well as a clear understanding of the utility and limitations of currently available diagnostic tests, is essential in reducing global disease burden.</span></span></span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"104 ","pages":"Article 102758"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9904520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antineoplastic effects of pharmacological inhibitors of aurora kinases in CSF3RT618I-driven cells","authors":"Natália Sudan Parducci ,&nbsp;Anali Del Milagro Bernabe Garnique ,&nbsp;Keli Lima ,&nbsp;Jorge Antonio Elias Godoy Carlos ,&nbsp;Natasha Peixoto Fonseca ,&nbsp;Lívia Bassani Lins de Miranda ,&nbsp;Bruna Oliveira de Almeida ,&nbsp;Eduardo Magalhães Rego ,&nbsp;Fabiola Traina ,&nbsp;João Agostinho Machado-Neto","doi":"10.1016/j.bcmd.2023.102799","DOIUrl":"https://doi.org/10.1016/j.bcmd.2023.102799","url":null,"abstract":"<div><p><span>Myeloproliferative neoplasms<span><span> (MPN) are consolidated as a relevant group of diseases<span> derived from the malfunction of the hematopoiesis process and have as a particular attribute the increased proliferation of myeloid </span></span>lineage<span>. Among these, chronic neutrophilic leukemia (CNL) is distinguished, caused by the T618I mutation of the </span></span></span><em>CSF3R</em><span> gene, a trait that generates ligand-independent receptor activation and downstream JAK2/STAT signaling. Previous studies reported that mutations in BCR::ABL1 and JAK2</span>^V617F<span> increased the expression of the aurora kinase A<span> (AURKA) and B (AURKB) in Ba/F3 cells and their pharmacological inhibition displays antineoplastic effects in human BCR::ABL1 and JAK2</span></span>^V617F positive cells. Delimiting the current scenario, aspects related to the AURKA and AURKB as a potential target in CSF3R^T618I<span>-driven models is little known. In the present study, the cellular and molecular effects of pharmacological inhibitors of aurora kinases, such as aurora A inhibitor I, AZD1152-HQPA, and reversine, were evaluated in Ba/F3 expressing the CSF3R</span>^T618I<span><span><span><span><span> mutation. AZD1152-HQPA and reversine demonstrated antineoplastic potential, causing a decrease in cell viability, </span>clonogenicity, and proliferative capacity. At molecular levels, all inhibitors reduced </span>histone H3<span> phosphorylation, aurora A inhibitor I and reversine reduced STAT5 phosphorylation, and AZD1152-HQPA and reversine induced </span></span>PARP1<span> cleavage and γH2AX expression. Reversine more efficiently modulated genes associated with cell cycle and apoptosis compared to other </span></span>drugs. In summary, our findings shed new insights into the use of AURKB inhibitors in the context of CNL.</span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"104 ","pages":"Article 102799"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49821171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A stepwise diagnostic approach for undiagnosed Anemia in children: A model for low-middle income country","authors":"Nihal Hussien Aly ,&nbsp;Mohsen Saleh Elalfy ,&nbsp;Safinaz Adel Elhabashy ,&nbsp;Nadia Mohamed Mowafy ,&nbsp;Roberta Russo ,&nbsp;Immacolata Andolfo ,&nbsp;Achille Iolascon ,&nbsp;Iman Ahmed Ragab","doi":"10.1016/j.bcmd.2023.102779","DOIUrl":"10.1016/j.bcmd.2023.102779","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Reaching a precise diagnosis in rare inherited anemia is extremely difficult and challenging, especially in areas with limited use of genetic&lt;span&gt; studies, which makes undiagnosed anemia a unique clinical entity in tertiary hematology centers. In this study, we aim at plotting a stepwise diagnostic approach in children with undiagnosed anemia while identifying indications for genetic testing.&lt;/span&gt;&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Patients and methods&lt;/h3&gt;&lt;p&gt;A one-year cross-sectional study involved 44 children and adolescents with undiagnosed anemia after undergoing an initial routine panel of investigations. They were classified based on mean corpuscular volume (MCV) into 3 groups: microcytic (&lt;em&gt;n&lt;/em&gt; = 19), normocytic (&lt;em&gt;n&lt;/em&gt; = 14) and macrocytic (&lt;em&gt;n&lt;/em&gt; = 11). An algorithm that included four levels of investigations was devised for each category.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;&lt;span&gt;&lt;span&gt;&lt;span&gt;After applying a systematic diagnostic approach, 33 patients (75 %) were diagnosed of whom 7 (15 %) had combined diagnoses, while 11 (25 %) patients remained undiagnosed. Based on the first, second, third and fourth levels of investigations, patients were diagnosed, respectively, as follows: of the 11 patients, 7 were microcytic, 3 normocytic and 1 macrocytic; of the 7 patients, 2 were microcytic, 2 normocytic, and 3 macrocytic; of 10 patients, 5 were microcytic, 4 normocytic and 1 macrocytic; finally, of the 16 patients, 8 were microcytic, 6 normocytic and 2 macrocytic. Numbers recorded appear higher than the actual number of the patients because some of them were diagnosed by more than one level of investigation. The diagnoses obtained in the microcytic group showed hemoglobinopathies, iron refractory &lt;/span&gt;iron deficiency anemia (IRIDA), membrane defects, &lt;/span&gt;sideroblastic anemia&lt;span&gt;&lt;span&gt;, hypo-transferrinemia, a combined diagnosis of sickle cell trait and pyropoikilocytosis. The diagnoses also showed a combined diagnosis of hereditary &lt;/span&gt;spherocytosis&lt;span&gt;&lt;span&gt; (HS) and alpha thalassemia&lt;span&gt; minor, and a combined diagnosis of iron deficiency anemia and beta thalassemia minor, while 15 % remained undiagnosed. In the normocytic group, the diagnosis revealed &lt;/span&gt;&lt;/span&gt;autosomal recessive&lt;span&gt;&lt;span&gt; (AR) HS, vitamin B12 deficiency, &lt;/span&gt;pyruvate kinase deficiency (PKD), congenital dyserythropoietic anemia (CDA) type I, &lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;Diamond Blackfan anemia&lt;span&gt;&lt;span&gt; and beta thalassemia major. In addition, it showed a combined diagnosis of AR HS and CDA type II&lt;span&gt;, a combined diagnosis of AR HS and PKD, and a combined diagnosis of dehydrated stomatocytosis (DHS) and G6PD carrier, meanwhile 20 % remained undiagnosed. Finally, the macrocytic group was diagnosed by vitamin B12 deficiency, sideroblastic anemia, PKD, a combined diagnosis of PKD and &lt;/span&gt;&lt;/span&gt;G6PD deficiency carrier, while 45 % remained undiagnosed.&lt;/span&gt;&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;Conducting a stepwise approac","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"103 ","pages":"Article 102779"},"PeriodicalIF":2.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9996941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic examination of hematological parameters in SARS-CoV-2 infection and COVID-19","authors":"Quan Sun ,&nbsp;Bryce Rowland ,&nbsp;Wanjiang Wang ,&nbsp;Tyne W. Miller-Fleming ,&nbsp;Nancy Cox ,&nbsp;Misa Graff ,&nbsp;Annika Faucon ,&nbsp;Megan M. Shuey ,&nbsp;Elizabeth E. Blue ,&nbsp;Paul Auer ,&nbsp;Yun Li ,&nbsp;Vijay G. Sankaran ,&nbsp;Alexander P. Reiner ,&nbsp;Laura M. Raffield","doi":"10.1016/j.bcmd.2023.102782","DOIUrl":"10.1016/j.bcmd.2023.102782","url":null,"abstract":"<div><p><span><span>People hospitalized with COVID-19 often exhibit altered hematological traits associated with disease prognosis (e.g., lower lymphocyte and platelet counts). We investigated whether inter-individual variability in baseline hematological traits influences risk of acute SARS-CoV-2 infection or progression to severe COVID-19. We report inconsistent associations between blood cell traits with incident SARS-CoV-2 infection and severe COVID-19 in UK Biobank and the Vanderbilt University Medical Center Synthetic Derivative (VUMC SD). Since genetically determined blood cell measures better represent cell abundance across the lifecourse, we also assessed the shared genetic architecture of baseline blood cell traits on COVID-19 related outcomes by </span>Mendelian randomization (MR) analyses. We found significant relationships between COVID-19 severity and mean sphered cell volume after adjusting for multiple testing. However, MR results differed significantly across different freezes of COVID-19 summary statistics and genetic correlation between these traits was modest (0.1), decreasing our confidence in these results. We observed overlapping genetic association signals between other hematological and COVID-19 traits at specific loci such as </span><span><em>MAPT</em></span> and <span><em>TYK2</em></span>. In conclusion, we did not find convincing evidence of relationships between the genetic architecture of blood cell traits and either SARS-CoV-2 infection or COVID-19 hospitalization, though we do see evidence of shared signals at specific loci.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"103 ","pages":"Article 102782"},"PeriodicalIF":2.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10507673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10012396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next generation sequencing (NGS) interest in deciphering erythrocyte molecular defects' association in red cell disorders: Clinical and erythrocyte phenotypes of patients with mutations inheritance in PIEZO1, Spectrin ß1, RhAG and SLC4A1","authors":"Benoit Allegrini ,&nbsp;Ludivine David NGuyen ,&nbsp;Morgane Mignotet ,&nbsp;Catherine Etchebest ,&nbsp;Odile Fenneteau ,&nbsp;Jessica Platon ,&nbsp;Anne Lambilliotte ,&nbsp;Hélène Guizouarn ,&nbsp;Lydie Da Costa","doi":"10.1016/j.bcmd.2023.102780","DOIUrl":"10.1016/j.bcmd.2023.102780","url":null,"abstract":"<div><p><span><span>We report here an instructive case referred at 16 months-old for exploration of hemolysis without anemia (compensated anemia with reticulocytosis). The biology tests confirmed the hemolysis with increased total and indirect bilirubin. The usual hemolysis diagnosis tests were normal (DAT, G6PD, PK, Hb electrophoresis) except </span>cytology<span> and ektacytometry suggesting an association of multiple red blood cell (RBC) membrane disorders. This led us to propose a molecular screening analysis using targeted-Next Generation Sequencing (t-NGS) with a capture technique on 93 genes involved in RBC<span> and erythropoiesis defects. We identified 4 missense heterozygous allelic variations, all of them were described without any significance (VUS) in the </span></span></span><em>SLC4A1</em>, <em>RhAG</em>, <em>PIEZO1</em> and <em>SPTB</em><span> genes. The study of the familial cosegregation and research functional tests allowed to decipher the role of at least two by two genes in the phenotype and the hemolytic disease<span> of this young patient. Specialized t-NGS panel (or virtual exome/genome sequencing) in a disease-referent laboratory and the motivated collaboration of clinicians, biologists and scientists should be the gold standard for improving the diagnosis of the patients affected with RBC diseases or rare inherited anemias.</span></span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"103 ","pages":"Article 102780"},"PeriodicalIF":2.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10368379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Up-regulation of microRNA 101-3p during erythropoiesis in β-thalassemia/HbE","authors":"Phatchariya Phannasil ,&nbsp;Chanyanat Sukhuma ,&nbsp;Donny Nauphar ,&nbsp;Khanita Nuamsee ,&nbsp;Saovaros Svasti","doi":"10.1016/j.bcmd.2023.102781","DOIUrl":"10.1016/j.bcmd.2023.102781","url":null,"abstract":"<div><p><span><span>Ineffective erythropoiesis is the main cause of anemia in β-thalassemia. The crucial hallmark of ineffective erythropoiesis is the high proliferation of </span>erythroblast<span>. microRNA<span> (miR/miRNA) involves several biological processes<span>, including cell proliferation and erythropoiesis. miR-101 was widely studied and associated with proliferation in several types of cancer. However, the miR-101-3p has not been studied in β-thalassemia/HbE. Therefore, this study aims to investigate the expression of miR-101-3p during erythropoiesis in β-thalassemia/HbE. The results showed that miR-101-3p was upregulated in the erythroblast of β-thalassemia/HbE patients on day 7, indicating that miR-101-3p may be involved with high proliferation in β-thalassemia/HbE. Therefore, the mRNA targets of miR-101-3p including </span></span></span></span><em>Rac1</em>, <span><em>SUB1</em></span>, <em>TET2</em>, and <em>TRIM44</em> were investigated to determine the mechanisms involved with high proliferation of β-thalassemia/HbE erythroblasts. <em>Rac1</em> expression was significantly reduced at day 11 in severe β-thalassemia/HbE compared to normal controls and mild β-thalassemia/HbE. <em>SUB1</em> gene expression was significantly lower in severe β-thalassemia/HbE compared to normal controls at day 9 of culture. For TET2 and TRIM44 expression, a significant difference was not observed among normal and β-thalassemia/HbE. However, the high expression of miR-101-3p at day 7 and these target genes was not correlated, suggesting that this miRNA may regulate ineffective erythropoiesis in β-thalassemia/HbE via other target genes.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"103 ","pages":"Article 102781"},"PeriodicalIF":2.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10049554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acquired elliptocytosis in chronic myeloid neoplasms: An enigmatic relationship to acquired red cell membrane protein and genetic abnormalities","authors":"Marshall A. Lichtman ,&nbsp;Ronald Sham","doi":"10.1016/j.bcmd.2023.102778","DOIUrl":"10.1016/j.bcmd.2023.102778","url":null,"abstract":"<div><p>Nineteen reports of 41 cases of acquired red cell elliptocytosis<span> associated with a chronic myeloid neoplasm are described. Although the majority of cases have an abnormality of the long arm of chromosome 20<span><span>, del(q20), several cases do not. Moreover, in one case a specific qualitative abnormality of red cell protein band 4.1(4.1R) was reported; however, several subsequent cases could find no abnormality of a red cell membrane protein or found a different abnormality, usually quantitative. Thus, this striking red cell phenotypic feature, acquired elliptocytosis, seen in myelodysplastic syndrome and other chronic </span>myeloproliferative diseases<span>, closely simulating the red cell phenotype of hereditary elliptocytosis, has an unexplained genetic basis, presumably as the result of an acquired mutation(s) in some chronic myeloid neoplasms.</span></span></span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"103 ","pages":"Article 102778"},"PeriodicalIF":2.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9986322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Essential genetic modifiers and their measurable impact in a community-recruited population analysis for non-severe hemoglobin E/β-thalassemia prenatal genetic counseling","authors":"Peerapon Wong ,&nbsp;Thirabhat Chitsobhak ,&nbsp;Suporn Jittasathian ,&nbsp;Chonnigarn Sirichantharawat ,&nbsp;Naritsara Cherdchoo ,&nbsp;Weerapong Prangcharoen ,&nbsp;Patcharanapa Jongautchariyakul ,&nbsp;Katechan Jampachaisri ,&nbsp;Akamon Tapprom ,&nbsp;Rawisut Deoisares ,&nbsp;Piyatida Chumnumsiriwath","doi":"10.1016/j.bcmd.2023.102765","DOIUrl":"10.1016/j.bcmd.2023.102765","url":null,"abstract":"<div><p><span>The study aimed to identify essential phenotype-modulating factors among the pre-existence of several important ones and clarify their measurable impact on the clinical severity of hemoglobin (Hb) E/β-thalassemia in a community-recruited population analysis. This prospective study was designed to compare modifiers between community- (less or no symptoms) and hospital-recruited individuals with Hb E/β-thalassemia. The formerly included couples previously assessed for prenatal thalassemia at-risk status at 42 community and 7 referral hospitals in Thailand through on-site investigations between June 2020 and December 2021. The control included Hb E/β-thalassemia patients undergoing transfusions. The Mahidol score classified disease severity. Beta-globin, α</span>⁰-thalassemia (-^SEA, -^THAI), α⁺-thalassemia (-α^3.7, -α^4.2), Hb Constant Spring (α^CS) alleles, rs766432 in <span><em>BCL11A</em></span>, rs9399137 in <em>HBS1L-MYB</em>, and rs7482144-<em>Xmn</em>I were evaluated. Modifiers were compared between 102 community- and 104 hospital-recruited cases. Alleles of β⁺, -^SEA, -α^3.7, α^CS, and a minor allele of rs9399137 were prevalent in the community and mild severity groups (<em>p</em><span> &lt; 0.05). Multiple linear regression analysis associated modulating alleles with −4.299 (-</span>^SEA), −3.654 (β⁺), −3.065 (rs9399137, C/C), −2.888 (α^CS), −2.623 (‐α^3.7), −2.361 (rs7482144, A/A), −1.258 (rs9399137, C/T), and −1.174 (rs7482144, A/G) severity score reductions (<em>p</em><span> &lt; 0.05). Certain modifiers must be considered in routine prenatal genetic counseling for Hb E/β-thalassemia.</span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"103 ","pages":"Article 102765"},"PeriodicalIF":2.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9997898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular characterization of a novel 83.9-kb deletion of the α-globin upstream regulatory elements by long-read sequencing","authors":"Jianjiang Feng ,&nbsp;Aiping Mao ,&nbsp;Ye Lu ,&nbsp;Haihong Shi ,&nbsp;Wanli Meng ,&nbsp;Chen Liang","doi":"10.1016/j.bcmd.2023.102764","DOIUrl":"10.1016/j.bcmd.2023.102764","url":null,"abstract":"<div><p><span><span>Inherited deletions of upstream regulatory elements of α-globin genes give rise to α-thalassemia, which is an autosomal recessive<span><span> monogenic disease. However, conventional thalassemia<span> target diagnosis often fails to identify these rare deletions. Here we reported a family with two previous pregnancies of Hb Bart's hydrops fetalis and was seeking for </span></span>prenatal diagnosis during the third pregnancy. Both parents had low level of </span></span>Hemoglobin A2<span> indicating α-thalassemia. Conventional Gap-PCR and PCR-reverse dot blot showed the father carried –</span></span>^SEA deletion but did not identify any variants in the mother. Multiplex ligation-dependent probe amplification identified a deletion containing two HS-40 probes but could not determine the exact region. Finally, a long-read sequencing (LRS)-based approach directly identified that the exact deletion region was chr16: 48,642-132,584, which was located in the α-globin upstream regulatory elements and named (αα)^JM<span> after the Jiangmen city. Gap-PCR and Sanger sequencing confirmed the breakpoint. Both the mother and fetus from the third pregnancy carried heterozygous (αα)</span>^JM, and the fetus was normally delivered at gestational age of 39 weeks. This study demonstrated that LRS technology had great advantages over conventional target diagnosis methods for identifying rare thalassemia variants and assisted better carrier screening and prenatal diagnosis of thalassemia.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"103 ","pages":"Article 102764"},"PeriodicalIF":2.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9997888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of SARS-CoV-2 in hemoglobinopathies is modified by age and race","authors":"Jennifer K. Frediani ,&nbsp;Ezra Pak-Harvey ,&nbsp;Richard Parsons ,&nbsp;Adrianna L. Westbrook ,&nbsp;William O'Sick ,&nbsp;Greg S. Martin ,&nbsp;Wilbur A. Lam ,&nbsp;Joshua M. Levy","doi":"10.1016/j.bcmd.2023.102756","DOIUrl":"10.1016/j.bcmd.2023.102756","url":null,"abstract":"<div><p>Prior literature has established a positive association between sickle cell disease and risk of contracting SARS-CoV-2. Data from a cross-sectional study evaluating COVID-19 testing devices (<em>n</em> = 10,567) was used to examine the association between underlying health conditions and SARS-CoV-2 infection in an urban metropolis in the southern United States. Firth's logistic regression was used to fit the model predicting SARS-CoV-2 positivity using vaccine status and different medical conditions commonly associated with COVID-19. Another model using the same method was built using SARS-CoV-2 positivity as the outcome and hemoglobinopathy presence, age (&lt;16 Years vs. ≥16 Years), race/ethnicity and comorbidities, including hemoglobinopathy, as the factors. Our first model showed a significant association between hemoglobinopathy and SARS-CoV-2 infection (OR: 2.28, 95 % CI: (1.17,4.35), <em>P</em> = 0.016). However, in the second model, this association was not maintained (OR: 1.35, 95 % CI: (0.72,2.50), <em>P</em> = 0.344). We conclude that the association between SARS-CoV-2 positivity and presence of hemoglobinopathies like sickle cell disease is confounded by race, age, and comorbidity status. Our results illuminate previous findings by identifying underlying clinical/demographic factors that confound the reported association between hemoglobinopathies and SARS-CoV-2. These findings demonstrate how social determinants of health may influence disease manifestations more than genetics alone.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"102 ","pages":"Article 102756"},"PeriodicalIF":2.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10198733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9659326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}