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1.
Zhonghua Xue Ye Xue Za Zhi ; 42(4): 313-317, 2021 Apr 14.
Artigo em Chinês | MEDLINE | ID: mdl-33979976

RESUMO

Objective: To analyze the DNA sequences and clinical phenotypes of four cases with rare thalassemia to improve its recognition and accurate diagnosis. Methods: The DNA sequence characteristics of four cases with rare thalassemia diagnosed from May 2014 to December 2019 were retrospectively analyzed, and related literature was reviewed. Results: The results of the routine gene test for thalassemia indicated that the common three type of deletion and three point mutations in hemoglobin alpha 1/2 (HBA1/A2) , and 16 point mutations in hemoglobin beta (HBB) gene were unable to be detected in cases 1-3, and case 4 was--SEA. However, the results of HBA1/A2 and HBB whole-genome sequencing revealed that the four cases had a point mutation of HBB:c.347C>A, HBB:c.1A>G, HBB:c.393T>G, and HBA2: c.301-1G>A (IVS II-142 G>A) , respectively. Meanwhile, the father, aunt, and grandfather of case 2 carried the HBB:c.1 A>G heterozygous point mutation. Conclusion: The novel mutations in HBB and HBA2 genes, resulting in a rare thalassemia, were revealed. Among them, the HBB:c.347C>A, HBB:c.1A>G, and HBA2:c.301-1G>A (IVS II-142 G>A) mutations were first reported in Chinese patients with thalassemia. Contrarily, HBB:c.393T>G mutation has not yet been recorded in the databases of human hemoglobin variants and thalassemia. The discovery of these novel nucleotide variants in this study would enrich the DNA mutation gene database of thalassemia.


Assuntos
Talassemia , Talassemia beta , Humanos , Mutação , Nucleotídeos , Estudos Retrospectivos , Talassemia/genética , Globinas beta/genética
2.
Med Sci Monit Basic Res ; 27: e929207, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33397841

RESUMO

As of November 25, 2020, over 60 million people have been infected worldwide by COVID-19, causing almost 1.43 million deaths. Puzzling low incidence numbers and milder, non-fatal disease have been observed in Thailand and its Southeast (SE) Asian neighbors. Elusive genetic mechanisms might be operative, as a multitude of genetic factors are widely shared between the SE Asian populations, such as the more than 60 different thalassemia syndromes (principally dominated by the HbE trait). In this study, we have plotted COVID-19 infection and death rates in SE Asian (SEA) countries against heterozygote HbE and thalassemia carrier prevalence. COVID-19 infection and death incidence numbers appear inversely correlated with the prevalence of HbE and thalassemia heterozygote populations. We posit that the evolutionary protective effect of the HbE and other thalassemic variants against malaria and the dengue virus may extend its advantage to resistance to COVID-19 infection, as HbE heterozygote population prevalence appears to be positively correlated with immunity to COVID-19. Host immune system modulations induce antiviral interferon responses and alter structural protein integrity, thereby inhibiting cellular access and viral replication. These changes are possibly engendered by HbE carrier miRNAs. Proving this hypothesis is important, as it may shed light on the mechanism of viral resistance and lead to novel antiviral treatments. This development can thus guide decision-making and action to prevent COVID-19 infection.


Assuntos
/genética , Resistência à Doença/genética , Suscetibilidade a Doenças , Hemoglobina E/genética , Antivirais/uso terapêutico , Grupo com Ancestrais do Continente Asiático , /imunologia , Dengue/genética , Heterozigoto , Humanos , Sistema Imunitário , Interferons , Malária/genética , Pandemias , Prevalência , Tailândia/epidemiologia , Talassemia/epidemiologia , Talassemia/genética
3.
J Int Med Res ; 48(12): 300060520967778, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33342339

RESUMO

INTRODUCTION: To evaluate a next-generation sequencing (NGS) workflow in the screening and diagnosis of thalassemia. METHODS: In this prospective study, blood samples were obtained from people undergoing genetic screening for thalassemia at our centre in Guangzhou, China. Genomic DNA was polymerase chain reaction (PCR)-amplified and sequenced using the Ion Torrent system and results compared with traditional genetic analyses. RESULTS: Of the 359 subjects, 148 (41%) were confirmed to have thalassemia. Variant detection identified 35 different types including the most common. Identification of the mutational sites by NGS were consistent with those identified by Sanger sequencing and Gap-PCR. The sensitivity and specificities of the Ion Torrent NGS were 100%. In a separate test of 16 samples, results were consistent when repeated ten times. CONCLUSION: Our NGS workflow based on the Ion Torrent sequencer was successful in the detection of large deletions and non-deletional defects in thalassemia with high accuracy and repeatability.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Talassemia , China , Testes Genéticos , Humanos , Mutação , Estudos Prospectivos , Análise de Sequência de DNA , Talassemia/diagnóstico , Talassemia/genética
4.
Mikrochim Acta ; 187(4): 238, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32189135

RESUMO

A simple probe pair was designed for the detection of hemoglobin E (HbE) genotype, a single-point mutation that leads to abnormal red blood cells commonly found in South East Asia. The key to differentiation is the use of a conformationally constrained peptide nucleic acid (PNA) that was immobilized on carboxymethylcellulose-modified paper. This was then used for target DNA binding and visualization by an enzyme-catalyzed pigmentation. The biotinylated target DNA bound to the immobilized probe was visually detected via alkaline phosphatase-linked streptavidin. This enzyme conjugate catalyzed the dephosphorylation of the substrate 5-bromo-4-chloro-3-indolyl phosphate, leading to a series of reactions that generate an intense, dark blue pigment. The test was validated with 100 DNA samples, which shows good discrimination among different genotypes (normal, HbE, and heterozygous) with 100% accuracy when optimal conditions of analysis were applied. The method does not require temperature control and can be performed at ambient temperature. This is an attractive feature for diagnosis in primary care, which accounts for a large part of affected population. Graphical abstract Schematic representation of a paper-based sensor for the detection of the gene Hemoglobin E. The interaction between an immobilized peptide nucleic acid and a DNA target leads to enzymatic pigmentation, allowing simple visual readout with up to 100% accuracy.


Assuntos
Colorimetria/métodos , Genótipo , Sondas de Ácido Nucleico/química , Ácidos Nucleicos Peptídicos , Talassemia/genética , Biotinilação , Carboximetilcelulose Sódica , DNA/metabolismo , Humanos , Sondas de Ácido Nucleico/metabolismo , Pigmentação
6.
Transfusion ; 60(1): 16-25, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31758587

RESUMO

BACKGROUND: Children with transfusion dependent anemia, such as sickle cell disease (SCD) and thalassemia, are at an increased risk for developing red blood cell (RBC) alloantibodies due to their lifelong need for transfusion therapy. With the advent of genotyping, extended RBC antigen typing can be incorporated into chronic transfusion therapy programs (CTTPs) to improve patient care and provide antigen matched blood for this population of patients. STUDY DESIGN AND METHODS: The hospital, blood center (BC), and hematology clinic caring for children requiring long-term transfusion support developed a CTTP. Genotyping was performed at entry to determine patient RBC antigen type. Limited versus extended antigen matching of transfusions was provided based on known RBC antibodies. RESULTS: Fifty patients with the following disorders were enrolled: 20 with SCD, 23 with thalassemia, and 7 with other disorders. At enrollment, nine (18%) had RBC alloantibodies, including six (30%) of patients with SCD and three (13%) with thalassemia. Two children developed antibodies after enrollment; one warm autoantibody following limited "CEK" matched RBCs and one patient with a hemizygous variant RHD allele developed anti-D. Six (30%) patients with SCD had variant RHCE alleles; two had homozygous variant alleles and four had a variant present along with a wild type allele. CONCLUSION: We demonstrate how a CTTP can be developed in a community hospital through collaboration with the blood supplier, hospital, and clinical care team. A model of incorporating RBC genotyping informs risk for alloimmunization and allows consideration of transfusion strategy for providing prophylactic antigen matched blood.


Assuntos
Alelos , Anemia Falciforme , Transfusão de Eritrócitos , Eritrócitos/metabolismo , Técnicas de Genotipagem , Sistema do Grupo Sanguíneo Rh-Hr , Talassemia , Adolescente , Anemia Falciforme/sangue , Anemia Falciforme/genética , Anemia Falciforme/terapia , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Isoanticorpos/sangue , Masculino , Sistema do Grupo Sanguíneo Rh-Hr/sangue , Sistema do Grupo Sanguíneo Rh-Hr/genética , Talassemia/sangue , Talassemia/genética , Talassemia/terapia
7.
Clin Biochem ; 76: 11-16, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31765637

RESUMO

OBJECTIVE: The clinical and hematologic features of thalassemia are due to different factors, and patients with identical genotypes may regularly exhibit variable severity. In the present work, one homozygous Chinese Gγ+(Aγδß)0-thalassemia case with an asymptomatic phenotype, which is contrary to traditional views, was identified. Analysis of the underlying causes of this rare clinical phenotype involved accurate genetic diagnosis and detection of several genetic modifications. METHODS: Six members of the proband's family were enrolled in the study. Hematological parameters and hemoglobin analysis results were recorded. A suspension-array system, multiplex gap-polymerase chain reaction (gap-PCR) and multiplex ligation-dependent probe amplification (MLPA) were used together to characterize genotypes. Sanger sequencing was utilized to examine the KLF1 gene and four primary fetal hemoglobin (Hb F)-associated single-nucleotide polymorphisms (SNPs). RESULTS: Four family members carried the Chinese Gγ+(Aγδß)0-thalassemia mutation, and a homozygous state was ultimately diagnosed for the proband. All of the Chinese Gγ+(Aγδß)0 mutation-positive cases were coinherited with the Southern Asian α-thalassemia deletion (- - SEA/αα). Two SNP variants, rs7776054 and rs9399137, in the HBS1L-MYB locus were detected in the proband. CONCLUSIONS: Thus far, this is the first study to describe the molecular characterization of a homozygous Chinese Gγ+(Aγδß)0-thalassemia patient who exhibits no clinical symptoms. Our findings suggest that coinheritance of α-thalassemia or HBS1L-MYB locus variants may affect the clinical severity of Chinese Gγ+(Aγδß)0-thalassemia. We conclude that the molecular examination of genetic determinants known to be associated with clinical outcomes in Chinese Gγ+(Aγδß)0-thalassemia should be emphasized.


Assuntos
Deleção de Genes , Homozigoto , Fenótipo , Talassemia/genética , Adulto , China , Feminino , Humanos , Masculino , Mutação , Gravidez
8.
Gene ; 726: 144226, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31669644

RESUMO

Hereditary spherocytosis is a congenital red blood cell disorder. Typical clinical manifestations include anemia, jaundice and splenomegaly, which overlap with the thalassemia phenotype. Therefore, in high prevalence thalassemia regions, hereditary spherocytosis cases are often misdiagnosed. Here, a case once diagnosed as thalassemia, based on preliminary clinical examinations, underwent genetic testing in our laboratory, where analysis of globin gene mutations proved negative. We conducted both clinical and genetic analyses on the patient and his family. We collected clinical data, performed erythrocyte membrane protein analysis by SDS-PAGE and sequenced the ANK1 gene. We also investigated pathogenic mechanisms through cDNA sequencing and literature studies. From patient clinical data, we diagnosed the patient with moderate to severe hereditary spherocytosis, rather than thalassemia. SDS-PAGE data showed that Ankyrin protein expression was reduced. Sequencing of genomic DNA identified a frameshift mutation (ANK1:c.2394_2397del CAGT). cDNA sequencing showed that the expression of a mutant allele was significantly decreased. Our study corrected a clinical misdiagnosis and confirmed the diagnosis of hereditary spherocytosis in this patient. Identification of such causative mutations is important for accurate downstream patient therapy and is critically important for the prevention/detection of another affected birth. Additionally, the disruption of mRNA transcribed from the mutant allele resulted in a significant reduction in Ankyrin expression and was speculatively considered the pathogenic mechanism behind this mutation.


Assuntos
Anquirinas/genética , Nucleotídeos/genética , Deleção de Sequência/genética , Esferocitose Hereditária/diagnóstico , Esferocitose Hereditária/genética , Alelos , Criança , Erros de Diagnóstico , Mutação da Fase de Leitura/genética , Humanos , Masculino , Mutação/genética , Fenótipo , RNA Mensageiro/genética , Talassemia/genética
9.
Biochemistry ; 59(1): 80-84, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31577420

RESUMO

Nonsense mutations that result in premature stop codons in the HBB gene cause ß-thalassemia. This disease is characterized by a reduced hemoglobin level due to the lack of ß-globin. Compounds that induce translational readthrough across the thalassemia-causing premature stop codon will have therapeutic benefits. Currently available molecules that induce translational readthrough lack specificity, and some of them show toxicity after prolonged use. In this study, we have developed an oligonucleotide-based approach to induce translational readthrough across the thalassemia-causing premature stop codon. Oligonucleotides that target HBB mRNA downstream of the premature stop codon could induce translational readthrough, generating a full-length ß-globin protein. We show this effect using fluorescence- and luminescence-based readthrough assays and by Western blot. Remarkably, the amount of oligonucleotide-induced translational readthrough product is comparable to that of the protein generated by normal translation when there was no premature stop codon. Thus, these oligonucleotides, with certain modifications, have the potential to be used as drugs for the treatment of ß-thalassemia. Also, this strategy can be extended to treat other genetic diseases caused by premature stop codons.


Assuntos
Códon de Terminação/metabolismo , Oligodesoxirribonucleotídeos/farmacologia , Oligonucleotídeos Antissenso/farmacologia , Biossíntese de Proteínas/efeitos dos fármacos , RNA Mensageiro/metabolismo , Globinas beta/genética , Células HEK293 , Humanos , Talassemia/genética
10.
Immunohematology ; 36(4): 137-145, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33544619

RESUMO

CONCLUSIONS: Blood transfusion, the main therapy for patients with severe thalassemia, is challenged by alloantibodies that can lead to hemolytic transfusion reactions. The use of prophylactic antigen-matched units is recommended, but serologic typing, before the first transfusion, is rarely performed and is not reliable after chronic transfusion. Patient DNA-based typing is a promising strategy, but clinical outcome data are lacking. The aim of this study was to determine the benefits of antigenmatched transfusion guided by DNA-based typing in terms of new alloantibody formation and increases in mean pretransfusion hemoglobin (Hb) levels. We performed DNA-based typing on samples from 24 transfusion-dependent patients with thalassemia who had no serologic phenotyping performed before the first transfusion. These patients were then transfused with antigen-matched donor RBC units that were typed serologically. New alloantibody formation and mean pre-transfusion Hb levels were evaluated after implementing this extended common antigen-matching transfusion protocol. Sixty-three percent of the patients in this study were diagnosed as having beta-thalassemia Hb E. Alloantibodies were already present in 87.5 percent (21/24) of these patients, and most of these antibodies were multiple and/ or unidentified. After the enrollment, there were 717 transfusion episodes comprising 1209 RBC units. The number of RBC units transfused to each patient ranged from 22 to 119 units. At the median duration of 25.5 months (range 10-34 months), no new alloantibodies were detected since the beginning of the protocol. Seventy-four transfusion episodes in six patients were crossmatch-positive due to autoantibodies (patients 2, 4, 8, 9, and 14) or anti-Chido (patient 18) that had been identified before the study. There were no hemolytic transfusion reactions in this study. Five patients (patients 1, 2, 12, 15, and 20) showed increased mean pre-transfusion Hb levels (≥1 g/dL) and one patient (patient 16) had longer intervals between transfusions (compared with those before the protocol), suggesting longer RBC survival, although there was no statistical difference in the whole group. Our study highlights the benefits of DNA-based typing in chronically transfused patients with thalassemia who had no phenotyping data before the first transfusion. Patient DNA-based typing for antigen-matched transfusion is safe in thalassemia and allows us to obtain better-matched blood units for complicated patients.


Assuntos
Tipagem e Reações Cruzadas Sanguíneas , Transfusão de Sangue , DNA , Eritrócitos/imunologia , Talassemia/sangue , Talassemia/terapia , Humanos , Isoanticorpos/imunologia , Talassemia/genética , Talassemia/imunologia
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 1933-1937, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31839062

RESUMO

OBJECTIVE: To investigate the level of serum microRNA-609 and its clinical prognostic value in patients with thalassemia. METHODS: One hundred and twenty-seven patients with thalassemia treated in our hospital from April 2017 to April 2018 were selected, 100 healthy persons were selected as control group. The changes of miR-609 were analyzed by RT-PCR, the relationship between miR-609 and clinical indicators of thalassemia was analyzed, and the prognostic risk factors of thalassemia were evaluated by multivariate logistic regression analysis. RESULTS: The relative expression level of miR-609 in thalassemia patients was 3.17±0.24, which was significantly higher than that in control group (P<0.05). The levels of ALT, Plt and MCH in patients with high expression of miR-609 were significantly higher than those in patients with low expression of miR-609 (P<0.05). The levels of Hb and sICAM-1 in patients with high expression of miR-609 were significantly lower than those in patients with low expression of miR-609 (P<0.05). There was no correlation between the level of miR-609 and the patient's sex, age and AST (P>0.05). The incidence rate of mild anemia in high expression group was significantly lower than that in low expression group (P<0.05). There was no correlation between the level of miR-609 and the incidence rate of moderate anemia (P>0.05). The number of patients with severe anemia in the miR-609 high expression group was higher than that in miR-609 low expression group (P<0.05). The incidence rate of dizziness, fatigue and fever in patients with miR-609 high expression group was significantly higher than those in patients with miR-609 low expression (P<0.05). There was no correlation between the level of miR-609 and the incidence rate of nausea in patients with thalassemia. ROC curve showed that the AUC value of microRNA-609 was 0.862, the sensitivity was 83.6%, and the specificity was 84.1%, which suggested that miR-609 had a high diagnostic value for thalassemia. Multivariate logistic regression analysis showed that MCH and mir-609 were risk factors for poor prognosis of thalassemia patients. CONCLUSION: The increased level of serum miR-609 in patients with thalassemia is a risk factor for poor prognosis and can be used as a reference index for evaluating the efficacy for patients.


Assuntos
Talassemia , Biomarcadores Tumorais , Humanos , MicroRNAs , Prognóstico , Curva ROC , Talassemia/genética
13.
Hemoglobin ; 43(4-5): 249-253, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31581858

RESUMO

This study assessed thalassemia and hemoglobinopathies in a group of the Tay ethnic minority. Participants included 289 women of reproductive-age who enrolled in a pilot screening program for thalassemia conducted at six communities of Thai Nguyen Province, northern Vietnam. Standard procedures including complete blood count (CBC), hemoglobin (Hb) and DNA analyses were performed for all samples. The prevalence of thalassemia in 289 Tay women was 15.6% (gene frequency 0.078) for α0-thalassemia (α0-thal), 10.0% (gene frequency 0.050) for α+-thal, 7.3% (gene frequency 0.036) for ß-thalassemia (ß-thal), 2.4% (gene frequency 0.012) for Hb Constant Spring [Hb CS; α142, Term→Gln, TAA>CAA (α2), HBA2: c.427T>C] and 1.7% (gene frequency 0.009) for Hb E [ß26(B8)Glu→Lys, GAG>AAG; HBB: c.79G>A]. Further analysis of ß-globin gene abnormalities identified four mutations including codons 41/42 (-TCTT) (HBB: c.126_129delCTTT), codon 17 (A>T) (HBB: c.52A>T), codons 71/72 (+A) (HBB: c.216_217insA), and -28 (A>G) (HBB: c.78A>G). The results hint at the remarkably high frequencies of severe forms of thalassemia that indicate a serious public health problem requiring further exploration, and most probably, also intervention within the country.


Assuntos
Hemoglobinopatias/etnologia , Grupos Minoritários , Talassemia/etnologia , Grupos Étnicos , Feminino , Frequência do Gene , Hemoglobinopatias/genética , Hemoglobinas Anormais , Humanos , Programas de Rastreamento , Mutação , Prevalência , Talassemia/genética , Vietnã/epidemiologia , Vietnã/etnologia , Talassemia alfa/etnologia , Talassemia alfa/genética , Globinas beta/genética , Talassemia beta/etnologia , Talassemia beta/genética
14.
J Genet Couns ; 28(6): 1148-1153, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31538382

RESUMO

The Military Health System (MHS) is a federally funded organization that provides care to active duty service members and their beneficiaries. Our objective was to determine what methods of prenatal screening are used by military treatment facilities (MTFs), assess variations between institutions, and determine how practice patterns align with national recommendations. We surveyed all MTFs offering comprehensive prenatal care (n = 49). Departments were asked about aneuploidy screening options, availability of diagnostic testing, and carrier screening. In all, 43 MTFs (88%) completed the survey. Most (39/43) patients were stratified based on risk (predominantly maternal age at delivery and history). The most commonly offered test was combined 1st/2nd trimester screening (59%). Sixty percent routinely offered diagnostic testing, though less than half routinely offered microarrays. The majority offered universal carrier screening for cystic fibrosis (98%) and complete blood count with screening for thalassemias and hemoglobinopathies (88%). At the time of data collection, only five facilities (12%) had implemented spinal muscular atrophy carrier screening. Considerable heterogeneity exists in prenatal aneuploidy testing and carrier screening within the MHS. Standardized guidelines, protocols, and laboratory support would improve processes across the system. Additional resources including genetic counseling support and provider education are needed.


Assuntos
Cobertura do Seguro , Medicina Militar/organização & administração , Diagnóstico Pré-Natal/métodos , Aneuploidia , Fibrose Cística/genética , Feminino , Aconselhamento Genético , Testes Genéticos , Hemoglobinopatias/genética , Humanos , Programas de Rastreamento , Idade Materna , Atrofia Muscular Espinal/genética , Gravidez , Cuidado Pré-Natal , Talassemia/genética , Estados Unidos
15.
Exp Gerontol ; 126: 110680, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31382012

RESUMO

Hemoglobins (Hbs) are heme-containing proteins binding oxygen, carbon monoxide, and nitric oxide. While erythrocytes are the most well-known location of Hbs, Hbs also exist in neurons, glia and oligodendroglia and they are primarily localized in the inner mitochondrial membrane of neurons with likely roles in cellular respiration and buffering protons. Recently, studies have suggested links between hypoxia and neurodegenerative disorders such as Alzheimer Disease (AD) and furthermore suggested involvement of Hbs in the pathogenesis of AD. While cellular immunohistochemical studies on AD brains have observed reduced levels of Hb in the cytoplasm of pre-tangle and tangle-bearing neurons, other studies on homogenates of AD brain samples observed increased Hb levels. This potential discrepancy may result from differential presence and function of intracellular versus extracellular Hbs. Intracellular Hbs may protect neurons against hypoxia and hyperoxia. On the other hand, extracellular free Hb and its degradation products may trigger inflammatory immune and oxidative reactions against neural macromolecules and/or damage the blood-brain barrier. Therefore, biological processes leading to reduction of Hb transcription (including clinically silent Hb mutations) may influence intra-erythrocytic and neural Hbs, and reduce the transport of oxygen, carbon monoxide and nitric oxide which may be involved in the (patho)physiology of neurodegenerative disorders such as AD. Agents such as erythropoietin, which stimulate both erythropoiesis, reduce eryptosis and induce intracellular neural Hbs may exert multiple beneficial effects on the onset and course of AD. Thus, evidence accumulates for a role of Hbs in the central nervous system while Hbs deserve more attention as possible candidate molecules involved in AD.


Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Hemoglobinas/fisiologia , Doença de Alzheimer/tratamento farmacológico , Animais , Barreira Hematoencefálica/metabolismo , Hipóxia Celular/fisiologia , Modelos Animais de Doenças , Eritropoetina/uso terapêutico , Hemoglobinas/genética , Humanos , Mutação , Neurônios/metabolismo , Talassemia/genética , Talassemia/psicologia
16.
Pathol Res Pract ; 215(10): 152578, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31451289

RESUMO

Epsilon gamma delta beta (εγδß)0 - thalassemia is a very rare disorder that results from large deletions in the ß-globin gene cluster which abolish all regional globin chain gene expression from that allele. Since it is an exceedingly rare cause of neonatal anemia and is not detected by routine newborn screening, it is usually not suspected clinically and commonly undiagnosed or misdiagnosed. In this study, we describe two patients diagnosed in our hospital with (εγδß)0-thalassemia based on the results obtained from DNA microarray analysis of their peripheral blood. The first patient of mixed European descent presented as a neonate with microcytic hemolytic anemia, hyperbilirubinemia, hypoglycemia and hypothermia, and was found to have a 2.2 Mb loss that included the entire ß-globin gene cluster and the locus control region (LCR). The second patient, also of mixed European descent, presented in the neonatal period with anemia, thrombocytopenia and cutaneous extramedullary hematopoiesis, and was found to have a 59 kb loss that included the ß-globin LCR, HBE1, HBG1, and HBG2 genes. Both cases highlight the importance of recognizing the clinical features of (εγδß)0-thalassemia and implementing appropriate testing to clarify the diagnosis and manage the condition.


Assuntos
Deleção de Sequência , Talassemia/diagnóstico , Talassemia/genética , Alelos , Análise Mutacional de DNA , Feminino , Humanos , Recém-Nascido , Masculino , Família Multigênica , Triagem Neonatal
17.
Mol Biol Rep ; 46(5): 5041-5048, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31273613

RESUMO

Thalassemia is one of the most common monogenic hereditary disorders. Despite noticeable advances made in prevention strategies, it is still highly prevalent in the Iranian population. A key approach to management and early diagnosis of the disease is through revealing the regions with high prevalence and determining common genetic and phenotypic diversity. In the current study Hemoglobin H (HbH) disease patients were analyzed as the most common form of thalassemia intermedia in Iran. A total of 80 patients suspected of being thalassemic according to their mild to moderate anemia, microcytosis and normal iron levels were included in this study at the hemoglobinopathy and thalassemia center of Ahvaz University of Medical Science. Patients were analyzed for hematological parameters and HbH mutations using Multiplex Gap Polymerase Chain Reaction and Multiplex Amplification Refractory Mutation System. Twelve mutations were detected in the studied population. The most common genotype was -α3.7/--MED (45%) followed by Homozygote αPoly A2 (17.5%). A total of ten different alpha-globin (α-globin) mutations were observed in patients which --MED, being the most common mutation (26.27%), followed by -α3.7 (24.37%) and αpolyA2(A>G) (18.12%). Hematological parameters such as Hb, MCV, MCH and HbH were assessed and results showed that they varied significantly among genotypes, adjusted to age and gender. This study reveals a highly diverse range of HbH patients different from what was thought in terms of both genotype and phenotype in the Khuzestan region of Iran. These findings could contribute to improve the thalassemia managing policies in this province.


Assuntos
Talassemia/genética , Talassemia alfa/genética , Adolescente , Adulto , Feminino , Estudos de Associação Genética/métodos , Genótipo , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Mutação , Fenótipo , Talassemia/metabolismo , Adulto Jovem , alfa-Globinas/genética , alfa-Globinas/metabolismo , Talassemia alfa/metabolismo , Talassemia beta/genética
18.
Int J Hematol ; 110(4): 474-481, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31240559

RESUMO

Molecular analysis of globin genes is an essential process for prenatal diagnosis (PND) of severe thalassemia. This study aimed to describe the molecular characteristics of thalassemia and hemoglobin (Hb) variants in PND program in northern Thailand. The type and frequency of globin gene mutations from 1290 couples at risk of fetal severe thalassemia diseases that were tested at Thalassemia Laboratory at Chiang Mai University from 2012 to 2017 were retrospectively reviewed. The PND program detected 444 (34.4%), 196 (15.2%) and 642 (49.8%) couples at risk of fetal Hb Bart's hydrops fetalis, beta-thalassemia major (BTM) and beta-thalassemia/Hb E disease, respectively. Coinheritance of more than one type of thalassemia was common and eight (0.6%) couples were at risk of two types of severe thalassemia. There were two types of alpha0-thalassemia; 893 (99.7%) Southeast Asian and 3 (0.3%) Thai deletions. Twenty beta-globin gene mutations were found with 94.3% of beta0-thalassemia. The codon 41/42 (- TTCT), codon 17 (A>T), IVS-I-1 (G>T) and codon 71/72 (+ A) comprised 90% of beta-thalassemia mutations. The study shows a high percentage of couples at risk of fetal Hb Bart's hydrops fetalis and BTM. The percentage of beta0-thalassemia is higher than those seen in other regions of Thailand.


Assuntos
Doenças Fetais/genética , Hemoglobinas/genética , Mutação , Diagnóstico Pré-Natal/métodos , Serviços Preventivos de Saúde , Talassemia/sangue , Talassemia/genética , Códon/genética , Feminino , Doenças Fetais/sangue , Doenças Fetais/classificação , Doenças Fetais/epidemiologia , Humanos , Hidropisia Fetal/sangue , Hidropisia Fetal/epidemiologia , Hidropisia Fetal/genética , Masculino , Gravidez , Estudos Retrospectivos , Risco , Índice de Gravidade de Doença , Tailândia/epidemiologia , Talassemia/classificação , Talassemia/epidemiologia
19.
Rinsho Ketsueki ; 60(5): 423-432, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31168008

RESUMO

Congenital hemolytic anemias are classified into three major categories: red cell membrane disorders, hemoglobinopathies, and red cell enzyme disorders. The membrane disorders are caused by abnormalities in erythrocyte membrane proteins and are often associated with disease-specific deformations of red blood cells. Historically, membrane disorders have been classified according to morphology. In recent years, however, comprehensive genetic analysis with next-generation sequencing has been performed in patients with hemolytic anemia for whom making an accurate diagnosis is difficult. These studies have led to the identification of new causative genes, but there have been inconsistent associations in some cases between the diagnosed disease and the patient's clinical manifestations. Thalassemia is a hemoglobinopathy caused by a quantitative abnormality of one or the other of the globin chains in hemoglobin. Most Japanese patients with thalassemia have mild forms of the disease, which is different from reports in other countries. However, with globalization, the proportion of Japanese patients with intermediate or severe anemia is increasing. Therefore, it is incumbent on hematologists in Japan to be knowledgeable regarding prenatal diagnosis of and gene therapy for thalassemia.


Assuntos
Membrana Eritrocítica/patologia , Talassemia/diagnóstico , Talassemia/genética , Humanos
20.
BMC Med Genet ; 20(1): 86, 2019 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-31113390

RESUMO

BACKGROUND: Southern China provinces have high incidence of thalassemia, however, sporadic cases can be found in northern China as well. METHODS: People resided in north China who were suspected to have thalassemia were detected mutations by gap-polymerase chain reaction (Gap-PCR) and reverse dot blot (RDB) analyses. Those with positive findings from 2012 to 2017 were further analyzed for basic clinical data and ancestral information either by medical records or by telephone follow-up or both. RESULTS: Most people enrolled in our study had no or mild symptoms. For those with positive gene findings, people originated from the north had higher percentage of ß-thalassemia gene mutations compared with those originated from the south (72.8% vs. 62.4%, χ2 = 9.92, P = 0.001). Analysis of the individual gene distribution of people from south and north areas did not show significant difference either in α- thalassemia (P = 0.221) or ß-thalassemia (P = 0.979). No significant difference was found in the frequency of α mutation in people living in different altitudes. However, for ß-thalassemia, the frequency of the 6 most common mutations was significantly different in people living in different provinces with altitude below 500 m, 500-1000 m, and above 1000 m (χ2 test, P < 0.05). CONCLUSION: Most of people in north China with thalassemia mutation gene were thalassemia carriers. People originated from the north had higher frequency of ß mutation than those originated from the south, but the north people had similar individual gene mutation profile compared with south people both for α and ß mutations. People lived in different altitudes had different spectrum of ß mutations.


Assuntos
Talassemia/genética , Adolescente , Adulto , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da Polimerase , Talassemia/epidemiologia , Adulto Jovem
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