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1.
Braz. j. biol ; 83: e246062, 2023. tab, graf
Artigo em Inglês | MEDLINE, LILACS, VETINDEX | ID: biblio-1339355

RESUMO

Abstract A group of inherited blood defects is known as Thalassemia is among the world's most prevalent hemoglobinopathies. Thalassemias are of two types such as Alpha and Beta Thalassemia. The cause of these defects is gene mutations leading to low levels and/or malfunctioning α and β globin proteins, respectively. In some cases, one of these proteins may be completely absent. α and β globin chains form a globin fold or pocket for heme (Fe++) attachment to carry oxygen. Genes for alpha and beta-globin proteins are present in the form of a cluster on chromosome 16 and 11, respectively. Different globin genes are used at different stages in the life course. During embryonic and fetal developmental stages, γ globin proteins partner with α globin and are later replaced by β globin protein. Globin chain imbalances result in hemolysis and impede erythropoiesis. Individuals showing mild symptoms include carriers of alpha thalassemia or the people bearing alpha or beta-thalassemia trait. Alpha thalassemia causes conditions like hemolytic anemia or fatal hydrops fetalis depending upon the severity of the disease. Beta thalassemia major results in hemolytic anemia, growth retardation, and skeletal aberrations in early childhood. Children affected by this disorder need regular blood transfusions throughout their lives. Patients that depend on blood transfusion usually develop iron overload that causes other complications in the body systems like renal or hepatic impairment therefore, thalassemias are now categorized as a syndrome. The only cure for Thalassemias would be a bone marrow transplant, or gene therapy with currently no significant success rate. A thorough understanding of the molecular basis of this syndrome may provide novel insights and ideas for its treatment, as scientists have still been unable to find a permanent cure for this deadly disease after more than 87 years since it is first described in 1925.


Resumo Um grupo de defeitos sanguíneos hereditários é conhecido como talassemia e está entre as hemoglobinopatias mais prevalentes do mundo. As talassemias são de dois tipos, como talassemia alfa e beta. As causas desses defeitos são as mutações genéticas que levam a níveis baixos e/ou proteínas de globina com mau funcionamento, respectivamente. Em alguns casos, uma dessas proteínas pode estar completamente ausente. As cadeias de globina α e β formam uma dobra ou bolsa de globina para a fixação de heme (Fe ++) para transportar oxigênio. Os genes das proteínas alfa e beta globina estão presentes na forma de um cluster nos cromossomos 16 e 11, respectivamente. Diferentes genes de globina são usados ​​em diferentes estágios do curso de vida. Durante os estágios de desenvolvimento embrionário e fetal, as proteínas γ globina se associam à α globina e, posteriormente, são substituídas pela proteína β globina. Os desequilíbrios da cadeia de globina resultam em hemólise e impedem a eritropoiese. Indivíduos que apresentam sintomas leves incluem portadores de talassemia alfa ou as pessoas com traços de talassemia alfa ou beta. A talassemia alfa causa condições como anemia hemolítica ou hidropsia fetal fatal, dependendo da gravidade da doença. A beta talassemia principal resulta em anemia hemolítica, retardo de crescimento e aberrações esqueléticas na primeira infância. As crianças afetadas por esse distúrbio precisam de transfusões de sangue regulares ao longo da vida. Os pacientes que dependem de transfusão de sangue geralmente desenvolvem sobrecarga de ferro que causa outras complicações nos sistemas do corpo, como insuficiência renal ou hepática, portanto as talassemias agora são classificadas como uma síndrome. A única cura para as talassemias seria um transplante de medula óssea ou terapia genética sem atualmente uma taxa de sucesso significativa. Uma compreensão completa da base molecular dessa síndrome pode fornecer novos insights e ideias para seu tratamento, já que os cientistas ainda não conseguiram encontrar uma cura permanente para essa doença mortal depois de mais de 87 anos desde que foi descrita pela primeira vez em 1925.


Assuntos
Humanos , Pré-Escolar , Talassemia/genética , Talassemia beta/genética , Hemoglobinas
2.
Hematology ; 27(1): 672-683, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35666669

RESUMO

Objectives: Thalassemia, the most common global monogenetic disorder, is highly prevalent in southern China. Epidemiological and molecular characterization of thalassemia is important for designing appropriate prevention strategies in high-risk areas, especially the border area of Guangxi-Yunnan-Guizhou province in southwestern China.Methods: We recruited 38812 reproductive age couples and screened them for thalassemia. Routine blood tests as well as hemoglobin components and levels were evaluated. In addition, suspected thalassemia were identified by gap polymerase chain reaction (Gap-PCR) and PCR-based reverse dot blot (PCR-RDB).Results: The overall prevalence of thalassemia was 26.76%. Specifically, incidences of α-thalassemia, ß-thalassemia, and concurrent α- and ß-thalassemia were 17.52%, 6.92%, and 2.32%, respectively. The diagnosed α-thalassemia anomalies were associated with six gene mutations and 25 genotypes. The ß-thalassemia anomalies were associated with 12 gene mutations and 15 genotypes. Moreover, among the 1799 concurrent mutated α- and ß-thalassemia genes, 95 different genotypes were identified. Couples in which both partners were positive for α-thalassemia and ß-thalassemia isotypes were 8.80% and 2.08%, respectively. The proportion of couples at a risk of having children with thalassemia major or intermedia was high.Conclusions: This study elucidates on the prevalence and molecular characterization of thalassemia in the border area of Guangxi-Yunnan-Guizhou provinces. These findings provide valuable baseline data for genetic counseling and prenatal diagnosis, with the overarching goal of preventing and controlling severe thalassemia.


Assuntos
Talassemia alfa , Talassemia beta , Criança , China/epidemiologia , Feminino , Genótipo , Humanos , Mutação , Gravidez , Prevalência , Talassemia alfa/diagnóstico , Talassemia alfa/epidemiologia , Talassemia alfa/genética , Talassemia beta/diagnóstico , Talassemia beta/epidemiologia , Talassemia beta/genética
3.
Sci Rep ; 12(1): 9907, 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35701592

RESUMO

Thalassemia is a group of common hereditary anemias that cause significant morbidity and mortality worldwide. However, precisely diagnosing thalassemia, especially rare thalassemia variants, is still challenging. Long-range PCR and long-molecule sequencing on the PacBio Sequel II platform utilized in this study could cover the entire HBA1, HBA2 and HBB genes, enabling the diagnosis of most of the common and rare types of thalassemia variants. In this study, 100 cases of suspected thalassemia were subjected to traditional thalassemia testing and third-generation sequencing for thalassemia genetic diagnosis. Compared with traditional diagnostic methods, an additional 10 cases of rare clinically significant variants, including 3 cases of structure variants and 7 cases of single nucleotide variations (SNVs) were identified, of which a case with - α3.7 subtype III (- α3.7III) was first identified and validated in the Chinese population. Other rare variants of 11.1 kb deletions (- 11.1/αα), triplicate α-globin genes (aaa3.7/αα) and rare SNVs have also been thoroughly detected. The results showed that rare thalassemia variants are not rare but have been misdiagnosed by conventional methods. The results further validated third-generation sequencing as a promising method for rare thalassemia genetic testing.


Assuntos
Talassemia alfa , Talassemia beta , Genótipo , Humanos , Mutação , Análise de Sequência de DNA , alfa-Globinas/genética , Talassemia alfa/diagnóstico , Talassemia alfa/epidemiologia , Talassemia alfa/genética , Talassemia beta/genética
4.
G Ital Cardiol (Rome) ; 23(6): 477-480, 2022 Jun.
Artigo em Italiano | MEDLINE | ID: mdl-35674039

RESUMO

Cardiovascular complications are among the main causes of mortality and morbidity in patients with thalassemia major. Iron-chelation therapy is essential to prevent the chronic iron overload linked to the need for transfusions and the consequent cardiac hemosiderosis. Despite the wide use of iron-chelation drugs, today it is still possible to find cases of severe iron accumulation. Furthermore, even regardless of iron overload and cardiac dysfunction, the thalassemic patient has a high arrhythmic burden, especially for supraventricular arrhythmias. There are still many doubts and open questions about the management of such patients, especially regarding the correct use of anticoagulant therapy and the best utilization of therapeutic strategies available for rhythm control. The case presented shows how the interventional approach with catheter ablation can be useful also in the acute phase when antiarrhythmic drugs are ineffective and it is not possible to wait for the iron-chelation therapy to take effect.


Assuntos
Cardiopatias , Sobrecarga de Ferro , Metais Pesados , Talassemia beta , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/terapia , Cardiopatias/complicações , Humanos , Ferro/uso terapêutico , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/tratamento farmacológico , Metais Pesados/uso terapêutico , Talassemia beta/tratamento farmacológico , Talassemia beta/terapia
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(3): 844-850, 2022 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-35680815

RESUMO

OBJECTIVE: To provide a research basis for a safe and effective cell therapy for ß-thalassemia through optimization of HS4 region of the third generation lentiviral vector for stable expression of ß-globin. METHODS: The human ß-globin HS4 region in the third generation lentiviral expression vector was optimized to construct the lenti-HBB, and the transcription and translation of ß-globin gene were analyzed by RT-PCR and Western blot after the transduction of lenti-HBB in MEL cell line. Furthermore, the erythroid differentiation of CD34+ cells which were transduced lentiviral virus carrying human ß-globin from normal human umbilical cord blood cells and peripheral blood cells of patients with ß-thalassemia major were confirmed by colony formation assay, cell smear assay and flow cytometry. The safety and effectiveness of the optimized lenti-HBB were verified by NSG mouse in vivo test. RESULTS: The human ß-globin was expressed stably in the MEL cells, and CD34+ cells from health umbilical cord blood as well as PBMC from patient with ß-thalassemia major transduced with lenti-HBB could be differentiated to mature red blood cells. The ß-globin expression and differentiation in CD34+ cells were demonstrated successfully in the NSG mouse for about 35 months after post-transplant. CONCLUSION: Stable ß-globin expression through the optimization of HS4 from CD34+ in the third generation lentiviral vector is safe and effective for patients with severe ß-thalassemia and other ß-globin abnormal diseases.


Assuntos
Globinas beta , Talassemia beta , Animais , Terapia Genética , Vetores Genéticos , Humanos , Lentivirus/genética , Leucócitos Mononucleares , Camundongos , Globinas beta/genética , Talassemia beta/genética , Talassemia beta/terapia
6.
Cells ; 11(11)2022 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-35681538

RESUMO

Autologous hematopoietic stem cell (HSC)-targeted gene therapy provides a one-time cure for various genetic diseases including sickle cell disease (SCD) and ß-thalassemia. SCD is caused by a point mutation (20A > T) in the ß-globin gene. Since SCD is the most common single-gene disorder, curing SCD is a primary goal in HSC gene therapy. ß-thalassemia results from either the absence or the reduction of ß-globin expression, and it can be cured using similar strategies. In HSC gene-addition therapy, patient CD34+ HSCs are genetically modified by adding a therapeutic ß-globin gene with lentiviral transduction, followed by autologous transplantation. Alternatively, novel gene-editing therapies allow for the correction of the mutated ß-globin gene, instead of addition. Furthermore, these diseases can be cured by γ-globin induction based on gene addition/editing in HSCs. In this review, we discuss HSC-targeted gene therapy in SCD with gene addition as well as gene editing.


Assuntos
Anemia Falciforme , Transplante de Células-Tronco Hematopoéticas , Talassemia beta , Anemia Falciforme/genética , Anemia Falciforme/metabolismo , Anemia Falciforme/terapia , Edição de Genes/métodos , Terapia Genética/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/metabolismo , Humanos , Globinas beta/genética , Talassemia beta/genética , Talassemia beta/metabolismo , Talassemia beta/terapia
8.
BMJ Case Rep ; 15(6)2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35688572

RESUMO

Solid masses of the ovaries raise the suspicion of malignancy or metastasis and require histological diagnosis. Extramedullary haematopoesis (EMH) is a rare histological finding of a mass of the adnexa. The sonographic pattern of EMH has rarely been described in the literature. Transvaginal biopsy of EMH has not been reported in the literature. We present a case of adnexal EMH in a patient affected with ß-thalassaemia, and we performed a narrative review. Only in our case, the sonographic pattern was described, and a transvaginal ultrasound-guided core biopsy was used. Assessing patients' medical history and correlating it to the findings of diagnostic imaging is of paramount importance when evaluating patients with adnexal masses. The correct interpretation of sonographic images can avoid unnecessarily invasive procedures. A transvaginal biopsy could be a safe, easy and well-tolerated method to gain definite histological diagnosis in cases where a primary ovarian malignancy is not suspected.


Assuntos
Doenças dos Anexos , Doenças Hematológicas , Hematopoese Extramedular , Neoplasias Ovarianas , Talassemia beta , Anexos Uterinos/patologia , Doenças dos Anexos/diagnóstico , Feminino , Doenças Hematológicas/patologia , Humanos , Neoplasias Ovarianas/patologia , Talassemia beta/complicações
9.
Sci Rep ; 12(1): 9762, 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35697769

RESUMO

This monocentric study conducted at the Pediatric and Adult Hemoglobinopathy Outpatient Units of the University Hospital of Essen summarizes the results of hemoglobinopathies diagnosed between August 2018 and September 2021, prior to the introduction of a general newborn screening (NBS) for SCD in Germany (October 2021). In total, 339 patients (pts.), 182 pediatric [50.5% males (92/182)] and 157 adult pts. [75.8% females (119/157)] were diagnosed by molecular analysis. The most common (parental) descent among affected pts. were the Middle Eastern and North African/Turkey (Turkey: 19.8%, Syria: 11.8%, and Iraq: 5.9%), and the sub-Saharan African region (21.3%). Median age at diagnosis in pediatric carriers [N = 157; 54.1% males (85/157)] was 6.2 yrs. (range 1 (months) mos.-17.8 yrs.) and 31 yrs. (range 18-65 yrs.) in adults [N = 53; 75.2% females (115/153)]. Median age at diagnosis of homozygous or compound-heterozygous disease in pediatric pts. (72% (18/25) females) was 3.7 yrs., range 4 mos.-17 yrs. (HbSS (N = 13): 2.5 yrs., range 5 mos.-7.8 yrs.; HbS/C disease (N = 5): 8 yrs., range 1-8 yrs.; homozygous/compound heterozygous ß-thalassemia (N = 5): 8 yrs., range 3-13 yrs.), in contrast to HbH disease (N = 5): 18 yrs. (median), range 12-40 yrs. Hemoglobinopathies represent a relevant health problem in Germany due to immigration and late diagnosis of second/third generation migrants. SCD-NBS will accelerate diagnosis and might result in reduction of disease-associated morbidity. However, diagnosis of carriers and/or disease-states (i.e. thalassemic syndromes) in newly immigrated and undiagnosed patients will further be delayed. A first major step has been taken, but further steps are required.


Assuntos
Anemia Falciforme , Hemoglobinopatias , Talassemia , Talassemia beta , Adulto , Criança , Feminino , Alemanha/epidemiologia , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/epidemiologia , Hemoglobinopatias/genética , Humanos , Recém-Nascido , Masculino , Triagem Neonatal/métodos , Turquia
10.
J Trop Pediatr ; 68(4)2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35708565

RESUMO

OBJECTIVES: To study the prevalence of anemia among healthy infants, and outcomes of giving a therapeutic trial of iron to anemic infants in thalassemia-endemic area. METHODS: A cross sectional study was conducted in 6-9-month-old, full-term healthy infants who attended the well child clinics at 2 tertiary care centers in southern Thailand. Complete blood count and serum ferritin were performed in every infant, and hemoglobin typing was performed only in anemic cases. All anemic infants were given a therapeutic trial of iron and categorized into either; iron responder (hemoglobin increased ≥ 1 g/dL) or iron non-responder (hemoglobin increased <1 g/dL) groups after one month of the therapeutic trial. Mean levels of hematological parameters, including the Mentzer index, were compared within the groups. RESULTS: A total of 620 infants were included in the study. From this, 230 infants (37%) were anemic for which iron deficiency contributed for 80% of the etiology. The iron responder group showed significant improvement in hematological parameters after a trial of iron, while there was no improvement in the iron non-responder group. Among iron responders, there were 31 out of 186 infants (16.6%) who had coexisting abnormal hemoglobin typing, and their post-treatment complete blood count still showed a mean corpuscular volume < 70, with a Mentzer index < 13. CONCLUSION: Iron deficiency remains a major cause of anemia among infants, and a therapeutic trial of iron is beneficial in this age group, even though thalassemia trait/hemoglobinopathy can co-exist.


Assuntos
Anemia Ferropriva , Talassemia , Talassemia beta , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/epidemiologia , Anemia Ferropriva/etiologia , Estudos Transversais , Hemoglobinas/análise , Humanos , Lactente , Ferro/uso terapêutico , Talassemia/diagnóstico , Talassemia/epidemiologia , Talassemia beta/complicações
11.
Iran J Kidney Dis ; 16(3): 188-194, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35714213

RESUMO

INTRODUCTION: Patients with ß -thalassemia major (ß -TM) had a high rate of glomerular dysfunction due to chronic anemia, iron overload, and chelation therapy. There is also evidence of proximal tubular damage, as almost all patients have various amounts of proteinuria. MicroRNAs are non-coding RNA molecules that regulate gene expression. In diabetes, a relative increase in renal microRNA-451 appeared to protect against diabetic kidney injury. This study aimed to investigate the association between miRNA-451 and the development of chronic kidney disease (CKD) in children with ß-TM. METHODS: This study included 60 pediatric patients with ß-TM and 30 healthy children as controls. We categorized patients into two groups according to the presence of CKD. Complete blood and reticulocyte counts, serum levels of ferritin, creatinine and glucose, and urine albumin/creatinine ratio (ACR) were measured. Plasma miRNA-451 expression level was measured by real-time quantitative reversed transcription PCR in all included children. RESULTS: miRNA-451 levels were significantly higher in ß-TM (25.326 ± 12.191) as compared with controls (9.453 ± 5.753) (P < .001). Patients with ß-TM and CKD had significantly lower miRNA-451 levels (19.72 ± 13.023) than those without CKD (30.933 ± 8.23). MiRNA-451 levels had significantly positive correlated with eGFR (r = 0.385 P < .05) and reticulocyte counts (r = 0.27, P < .05). Linear logistic regression analysis showed that low plasma microRNA-451 was a significant independent predictor of CKD. CONCLUSION: miRNA-451 has a protective role against CKD development, and low plasma expression levels are associated with CKD in children with ß-TM  DOI: 10.52547/ijkd.6756.


Assuntos
MicroRNAs , Insuficiência Renal Crônica , Talassemia beta , Criança , Creatinina , Taxa de Filtração Glomerular/fisiologia , Humanos , Testes de Função Renal , MicroRNAs/genética , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/genética , Talassemia beta/complicações , Talassemia beta/genética
12.
Lancet ; 399(10343): 2310-2324, 2022 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-35691301

RESUMO

Thalassaemia is a diverse group of genetic disorders with a worldwide distribution affecting globin chain synthesis. The pathogenesis of thalassaemia lies in the unbalanced globin chain production, leading to ineffective erythropoiesis, increased haemolysis, and deranged iron homoeostasis. The clinical phenotype shows heterogeneity, ranging from close to normal without complications to severe requiring lifelong transfusion support. Conservative treatment with transfusion and iron chelation has transformed the natural history of thalassaemia major into a chronic disease with a prolonged life expectancy, albeit with co-morbidities and substantial disease burden. Curative therapy with allogeneic haematopoietic stem cell transplantation is advocated for suitable patients. The understanding of the pathogenesis of the disease is guiding therapeutic advances. Novel agents have shown efficacy in improving anaemia and transfusion burden, and initial results from gene therapy approaches are promising. Despite scientific developments, worldwide inequality in the access of health resources is a major concern, because most patients live in underserved areas.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Talassemia , Talassemia beta , Globinas , Humanos , Ferro , Talassemia/complicações , Talassemia/terapia , Talassemia beta/complicações , Talassemia beta/terapia
13.
BMC Pediatr ; 22(1): 344, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35705926

RESUMO

BACKGROUND: Iron overload (IO) is a complication in transfusion dependent beta thalassaemia (TDT). Pathogenic variants in genes involving iron metabolism may confer increased risk of IO. The objective of this study was to determine the magnitude of the cardiac and hepatic IO and determine whether pathogenic variants in HFE, SLC40A1 and TFR2 genes increase the risk of IO in a cohort of TDT patients in Sri Lanka. MATERIALS AND METHODS: Fifty-seven (57) patients with TDT were recruited for this study. Serum ferritin was done once in 3 months for a period of one year in all. Those who were ≥ 8 years of age (40 patients) underwent T2* MRI of the liver and heart. Fifty-two (52) patients underwent next generation sequencing (NGS) to identify pathogenic variants in HBB, HFE, SLC40A1 and TFR2 genes. RESULTS: The median age of the patients of this cohort was 10 years. It comprised of 30 (52.6%) boys and 27 (47.4%) girls. The median level of serum ferritin was 2452 ng/dl. Hepatic IO was seen in 37 (92.5%) patients and cardiac IO was seen in 17 (42.5%) patients. There was no statistically significant correlation between serum ferritin and hepatic or cardiac IO. Thirty-two (61.5%), 18 (34.6%), 2 (3.8%) of patients were homozygotes, compound heterozygotes and heterozygotes for pathogenic variants in the HBB gene. Eight (15.4%) and 1 (1.9%) patients were heterozygotes for pathogenic and likely pathogenic variants of HFE genes respectively. There were no pathogenic variants for the TfR2 and SLC40A1 genes. The heterozygotes of the pathogenic variants of the HFE were not at increased risk of IO. CONCLUSIONS: Cardiac T2* MRI helps to detect cardiac IO in asymptomatic patients. It is important to perform hepatic and cardiac T2* MRI to detect IO in patients with TDT. There was no statistically significant correlation between pathogenic variants of HBB and HFE genes with hepatic and cardiac IO in this cohort of patients.


Assuntos
Proteínas de Transporte de Cátions/genética , Proteína da Hemocromatose , Sobrecarga de Ferro , Receptores da Transferrina , Globinas beta/genética , Talassemia beta , Criança , Feminino , Ferritinas , Proteína da Hemocromatose/genética , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/genética , Masculino , Mutação , Receptores da Transferrina/genética , Sri Lanka , Talassemia beta/complicações , Talassemia beta/genética , Talassemia beta/terapia
14.
Ital J Pediatr ; 48(1): 105, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35725492

RESUMO

BACKGROUND: Beta thalassemia major (ß-TM) is a common cause of skeletal morbidity and is associated with increased bone fracture risk, particularly in inadequately transfused children. The aim of this study was to investigate some potential biochemical markers as possible early predictors of BMD variations in children with ß-TM. METHODS: The study included 38 children with ß-TM and 40 sex-age matched controls. All patients were subjected to BMD assessment by dual-energy X-ray absorptiometry (DEXA). Serum beta-crosslaps (beta-CTx), osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B ligand (RANKL), urinary deoxypyridinoline (DPD) and ferritin levels were compared between the groups. RESULTS: Serum OPG levels were significantly lower in thalassemic children than in controls. The mean ratio of RANKL/OPG was significantly higher in the thalassemic patients than in the control group. Osteoporosis was detected in 10 (3 female and 7 male) of 38 patients (26.3%) according to the femur Z score and in 6 of them (4 male and 2 female) (15.8%) according to the spine Z score. CONCLUSIONS: Serum OPG concentrations can be used as a biochemical marker in screening patients with beta-thalassemia major for the development of osteoporosis.


Assuntos
Osteoporose , Talassemia beta , Biomarcadores , Densidade Óssea , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Osteoporose/diagnóstico , Osteoporose/etiologia , Talassemia beta/complicações , Talassemia beta/diagnóstico
15.
Clin Lab ; 68(5)2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35536084

RESUMO

BACKGROUND: Thalassemia carrier couples play an important role in increasing thalassemia patients. The study of thalassemia genotypes in carrier couples is also effective in improving genetic counseling for them. The aim of this study was to investigate the prevalence of thalassemia mutations and genotypes in couples. METHODS: This cross-sectional study was performed on 241 couples who were suspected of thalassemia from April 2018 to March 2020 in Lorestan province. Statistical analysis of data was performed using SPSS software 16.0 (SPSS Inc., Chicago, IL, USA). Online tools such as www.ithanet.eu/db/ithagenes and http://globin.bx.psu.edu/ hbvar/menu.html were also used to match patients' mutations with known cases. RESULTS: IVSII-1 (G>A), CD36-37 (-T), IVSI-110 (G>A), --Med, and α3.7 were the most common mutations in the beta and alpha genes, respectively. IVSII-1 (G>A) ß0/ß (26.1%), CD36-37 (-T) ß0/ß (21.1%), and IVSI-110 (G>A) ß0/ß (10.3%) genotypes were the most common in women. The frequency of these genotypes in men were 24.8%, 28.6%, and 12.8%, respectively. Among alpha thalassemia carriers, the α3.7α/α α genotype had the highest frequency among women (3.7%) and men (5.3%). Alpha and beta-thalassemia were 15 and 13 times higher in related women and 18 and 9 times higher in related men than non-related ones, respectively. This difference was statistically significant (p < 0.001). In addition, 12.8% of fetuses were thalassemia major, 31.9% beta thalassemia minor, and 10.3% normal. CONCLUSIONS: Thalassemia screening in related couples plays an important role in reducing thalassemia major infants.


Assuntos
Talassemia alfa , Talassemia beta , Estudos Transversais , Testes Diagnósticos de Rotina , Feminino , Genótipo , Humanos , Masculino , Mutação , Gravidez , Talassemia alfa/diagnóstico , Talassemia beta/diagnóstico , Talassemia beta/genética
16.
Front Endocrinol (Lausanne) ; 13: 878680, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35600576

RESUMO

Background: Glycosylated hemoglobin A1c (HbA1c) is an important means of monitoring blood glucose and diagnosing diabetes. High-performance liquid chromatography (HPLC) is the most widely used method to detect HbA1c in clinical practice. However, the results of HbA1c by HPLC are susceptible to hemoglobinopathy. Here, we report a case of discordantly low HbA1c with an abnormal chromatogram caused by rare ß-thalassemia. Case Description: A 36-year-old Tujia Chinese woman presented with an abnormally low HbA1c level of 3.4% by HPLC in a health check-up. The chromatogram of HbA1c showed an abnormal peak. Fasting blood glucose, routine blood tests and serum bilirubin were normal. Her body mass index was 27.86 kg/m2. Hemoglobin electrophoresis showed low hemoglobin A and abnormal hemoglobin ß-chain variants. The thalassemia gene test suggested a rare type of ß-thalassemia (gene sequencing HBB: c.170G>A, Hb J-Bangkok (GGC->GAC at codon 56) in a beta heterozygous mutation). Glycated albumin (GA) was slightly increased. Oral glucose tolerance tests (OGTT) and insulin release tests indicated impaired glucose tolerance and insulin resistance. The hematologist advised follow-up visits. The endocrinologist recommended that the patient adopt lifestyle intervention. Three months later, GA returned to normal, and impaired glucose tolerance and insulin resistance improved. Conclusions: Clinically silent ß-thalassemia may lead to low HbA1c values and abnormal chromatograms by HPLC. In these circumstances, differential diagnosis is important. Checking the chromatogram may be helpful in interpreting HbA1c as well as identifying hemoglobinopathy. Further tests, such as GA, OGTT, hemoglobin electrophoresis and genetic tests, are needed for differential diagnosis.


Assuntos
Intolerância à Glucose , Hemoglobinopatias , Hemoglobinas Anormais , Resistência à Insulina , Talassemia beta , Adulto , Glicemia , China , Feminino , Hemoglobina A Glicada/análise , Testes Hematológicos , Hemoglobinas Anormais/análise , Hemoglobinas Anormais/química , Hemoglobinas Anormais/genética , Humanos , Tailândia , Talassemia beta/diagnóstico
17.
Dental Press J Orthod ; 27(2): e22205, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35613245

RESUMO

OBJECTIVE: The present study aimed to assess the morphology of symphysis and alveolar bone thickness (ABT) surrounding mandibular incisors in thalassemic patients, as compared to unaffected individuals. METHODS: This case-control study was conducted on lateral cephalograms of 60 thalassemic and 60 unaffected patients with Class II malocclusion seeking orthodontic treatment at Dental School, Shiraz University of Medical Sciences. The sample was divided into three subgroups including hyperdivergent, normodivergent, and hypodivergent, according to the Jarabak index. Symphysis dimensions and alveolar bone thickness surrounding mandibular incisors were measured using AutoCad software. Finally, the correlation between alveolar bone thickness and symphysis morphology was assessed. RESULTS: In general, chin dimensions and bone thickness at different levels of mandibular incisor roots (cervical, middle, apical) were smaller in thalassemic adolescents than controls. Concerning the total sample as well as the normodivergent subgroup, significantly lower values were observed in thalassemic patients for symphysis width, total ABT at the cervical, and lingual ABT at the apical root area compared to controls (p < 0.05). The hypodivergent growth pattern was not associated with any statistical differences between the groups (p> 0.05). In both thalassemic and control subjects, symphysis width showed a weak to moderate positive correlation with ABT of lower incisors (p< 0.05), whereas symphysis height showed a moderate positive correlation with cervical ABT in only ß-thalassemia patients (p< 0.05). CONCLUSIONS: Compared to controls, ß-thalassemia patients showed thinner alveolar bone at different levels of lower incisor roots and smaller symphysis dimensions. There were significant correlations between symphysis dimensions and alveolar bone thickness of mandibular incisors in the sample.


Assuntos
Talassemia beta , Adolescente , Estudos de Casos e Controles , Cefalometria/métodos , Queixo/anatomia & histologia , Tomografia Computadorizada de Feixe Cônico , Humanos , Incisivo/diagnóstico por imagem , Mandíbula/anatomia & histologia , Mandíbula/diagnóstico por imagem , Talassemia beta/complicações , Talassemia beta/diagnóstico por imagem
18.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(2): 252-257, 2022 Feb 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-35545416

RESUMO

ß-thalassemia (ß-thal) is one of the most common genetic diseases in the world, its pathogenesis is extremely complex and there is no effective treatment at present. The birth of children with moderate and severe ß-thal brings economic pressure to families, social medical and health services. Long noncoding RNA (lncRNA) is a type of noncoding protein transcripts with a length greater than 200 nucleotides, which is involved in a variety of biological processes, such as cell proliferation, differentiation and chromosome variation and plays an important role in the epigenetic and post-transcriptional regulation of genes. It has potential value in the diagnosis, prevention and treatment of ß-thal. LncRNA possesses the characteristics such as tissue specificity, cell specificity, developmental stage specificity, space-time specificity and disease specificity, and its complex interaction network has become a challenge to translate research results into clinical practice. Taking lncRNA as an entry point, in-depth understanding of the function of lncRNA in ß-thal and explanation of its related regulatory mechanisms will provide theoretical basis for targeting treatment of ß-thal, which can improve the diagnosis and treatment of ß-thal.


Assuntos
RNA Longo não Codificante , Talassemia beta , Diferenciação Celular , Criança , Regulação da Expressão Gênica , Humanos , RNA Longo não Codificante/genética , Talassemia beta/diagnóstico , Talassemia beta/genética , Talassemia beta/terapia
19.
Sci Rep ; 12(1): 8071, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35577924

RESUMO

The involvement of circRNAs in ß-thalassemia and their actions on fetal hemoglobin (HbF) is unclear. Here, the circRNAs in ß-thalassemia carriers with high HbF levels were comprehensively analyzed and compared with those of healthy individuals. Differential expression of 2183 circRNAs was observed and their correlations with hematological parameters were investigated. Down-regulated hsa-circRNA-100466 had a strong negative correlation with HbF and HbA2. Bioinformatics was employed to construct a hsa-circRNA-100466­associated competing endogenous RNA (ceRNA) network to identify hub genes and associated miRNAs. The hsa-circRNA-100466▁miR-19b-3p▁SOX6 pathway was identified using both present and previously published data. The ceRNA network was verified by qRT-PCR analysis of ß-thalassemia samples, RNA immunoprecipitation of K562 cell lysates, and dual-luciferase reporter analysis. qRT-PCR confirmed that hsa-circRNA-100466 and SOX6 were significantly down-regulated, while miR-19b-3p was up-regulated. Hsa-circRNA-100466, miR-19b-3p, and SOX6 were co-immunoprecipitated by anti-argonaute antibodies, indicating involvement with HbF induction. A further dual-luciferase reporter assay verified that miR-19b-3p interacted directly with hsa-circRNA-100466 and SOX6. Furthermore, spearman correlation coefficients revealed their significant correlations with HbF. In conclusion, a novel hsa-circRNA-100466▁miR-19b-3p▁SOX6 pathway was identified, providing insight into HbF induction and suggesting targets ß-thalassemia treatment.


Assuntos
MicroRNAs , Talassemia beta , Biologia Computacional , Hemoglobina Fetal/genética , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA/genética , RNA/metabolismo , RNA Circular/genética , Talassemia beta/genética
20.
J Int Med Res ; 50(5): 3000605221099013, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35549527

RESUMO

ß-thalassemia (ß-thal) is one of the most prevalent inherited blood disorders in Ganzhou, south China. Next-generation sequencing was used to screen for thalassemia carriers in the general population. During the screening, we identified a novel ß-thal variant in a 46-year-old Chinese man, which was validated by Sanger sequencing. Based on the patient's clinical data, this novel mutation was classified as severe ß0. However, the patient was mildly anemic (hemoglobin, 89 g/L), which was inconsistent with typical ß0 carrier characteristics. On further evaluation, quantitative PCR indicated the presence of six α genes, while molecular analysis and pedigree analysis revealed the coexistence of αααanti3.7 and αααanti4.2. Therefore, we report a novel ß-thal variant combined with six α genes. We describe the patient's clinical phenotype and the process of molecular diagnosis. This case extends the spectrum of thalassemia variants.


Assuntos
Globinas beta , Talassemia beta , Alelos , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação/genética , Fenótipo , Globinas beta/genética , Talassemia beta/diagnóstico , Talassemia beta/genética
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