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1.
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
2.
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
4.
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
6.
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
7.
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
8.
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
9.
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
10.
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
11.
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
12.
Ann Hematol ; 98(8): 1835-1844, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30953085

RESUMO

The manual verification of gene tests is time-consuming and error prone. In this study, we try to explore a high-efficiency, clinically useful auto-verification system for gene detection of thalassemia. A series of verification elements were rooted in the auto-verification system. Consistency check was applied initially as one of the essential elements in our study. One hundred twenty-four archived cases were used to choose the consistency-check rules' indices from routine blood examination and hemoglobin electrophoresis by the receiver operating characteristic curves. Rule 1 and rule 2 established by the chosen indices were compared by their passing rate, consistency with manual validation, and error rate. Finally, 748 cases were used for verifying the system's feasibility by evaluating the passing rate, turn-around time (TAT), and error rate. The rule 2 had a higher passing rate (67.7% vs. 50.8%) and consistency (0.623 vs. 0.364) than the rule 1 with an error rate of zero. In a "live" valuation, the auto-verification system can reduce the TAT and error rate of verification by 51.5% and 0.13%, respectively, with a high passing rate of 82.8%. The auto-verification system for gene detection of thalassemia in this study can shorten the validation time, reduce errors, and enhance efficiency.


Assuntos
Testes Genéticos/normas , Talassemia/diagnóstico , Talassemia/genética , alfa-Globinas/genética , Globinas beta/genética , Algoritmos , Feminino , Deleção de Genes , Expressão Gênica , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Controle de Qualidade , Curva ROC , Talassemia/classificação , Talassemia/patologia , alfa-Globinas/deficiência , Globinas beta/deficiência
13.
Artigo em Inglês | MEDLINE | ID: mdl-30849277

RESUMO

Previous studies reported that detection of polymorphisms inherited through paternal model could be potential markers for the Non-Invasive Prenatal Diagnosis (NIPD) of ß-thalassemia. The aim of the current study was to find out the associations of rs10768683 and rs968857 with transfusion-dependent thalassemia (TDT) in a southern Iranian population. A total of 175 subjects were investigated, divided into patients with TDT as case group (n = 75) and healthy people as control group (n = 100). Genomic DNAs were extracted from peripheral blood using salting out procedure. Genotyping rs10768683 and rs968857 was carried out by ARMS-PCR, then statistical analyses were assessed using SPSS, and Medcalc ver. 18 software. Data showed that rs10768683 was statistically significant in co-dominant model of inheritance (P = 0.025, OR = 2.11 [1.08-4.15]) and genotype frequencies of CG among controls and cases were 0.68 and 0.80, respectively. However, according to genotype frequencies, there was no association between rs968857 and TDT among cases and healthy controls in any models of inheritance. In conclusion, the present study showed the association of rs10768683 with major ß-thalassemia through ARMS-PCR technique.


Assuntos
Polimorfismo Genético/genética , Talassemia/genética , Transfusão de Sangue , Genótipo , Humanos , Irã (Geográfico) , Reação em Cadeia da Polimerase , Talassemia/sangue
14.
Mol Med Rep ; 19(4): 2837-2848, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30720081

RESUMO

Thalassemia is caused by complex mechanisms, including copy number variants (CNVs) and single nucleotide variants (SNVs). The CNV types of α­thalassemia are typically detected by gap­polymerase chain reaction (PCR). The SNV types are detected by Sanger sequencing. In the present study, a novel method was developed that simultaneously detects CNVs and SNVs by multiplex PCR and next­generation sequencing (NGS). To detect CNVs, 33 normal samples were used as a cluster of control values to build a baseline, and the A, B, C, and D ratios were developed to evaluate­SEA, ­α4.2, ­α3.7, and compound or homozygous CNVs, respectively. To detect other SNVs, sequencing data were analyzed using the system's software and annotated using Annovar software. In a test of performance, 128 patients with thalassemia were detected using the method developed and were confirmed by Sanger sequencing and gap­PCR. Four different CNV types were clearly distinguished by the developed algorithm, with ­SEA, ­α3.7, ­α4.2, and compound or homozygous deletions. The sensitivities for each CNV type were 96.72% (59/61), 97.37% (37/38), 83.33% (10/12) and 95% (19/20), and the specificities were 93.94% (32/33), 93.94% (32/33), 100% (33/33) and 100% (33/33), respectively. The SNVs detected were consistent with those of the Sanger sequencing.


Assuntos
Variações do Número de Cópias de DNA , Sequenciamento de Nucleotídeos em Larga Escala , Reação em Cadeia da Polimerase Multiplex , Polimorfismo de Nucleotídeo Único , Talassemia/diagnóstico , Talassemia/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Substituição de Aminoácidos , Criança , Pré-Escolar , Biologia Computacional/métodos , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Análise de Sequência de DNA , Adulto Jovem , alfa-Globinas/genética , Globinas beta/genética
15.
Transfus Med ; 29(3): 185-192, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30740798

RESUMO

OBJECTIVES: To assess current knowledge of National Heart, Lung and Blood Institutes (NHLBI) and Thalassemia International Federation (TIF) recommendations, blood banking practices and perceived challenges among transfusion services in the management of patients with haemoglobinopathies. BACKGROUND: Previous reports have demonstrated variations in transfusion practices for sickle cell disease (SCD) and thalassemia patients. Recently, NHLBI/TIF have provided transfusion recommendations for patients with haemoglobinopathies. METHODS: A cross-sectional survey was conducted of transfusion services from the state of Georgia previously identified as having SCD/thalassemia populations. The survey assessed transfusion service practices in pre-transfusion testing and blood product selection; awareness/implementation of NHLBI/TIF transfusion-based recommendations and perceived challenges in transfusing haemoglobinopathy patients. RESULTS: Responses were received from 35 of 49 (71%) institutions. Only institutions indicating transfusing SCD or thalassemia patients (32) were included in analysis. Seventy-one percent of non-sickle cell treatment centres (SCTCs) and 20% of non-thalassemia treatment centres follow NHLBI and TIF recommendations to perform a red blood cell phenotype beyond ABO/Rh(D) and provide Rh and Kell prophylactically matched units for SCD and thalassemia patients, respectively. Forty percent of institutions (33% of non-SCTCs) employ RBC genotyping to evaluate the red cell phenotype for SCD patients. Over 77% of institutions do not utilise a reliable method to identify SCD patients prior to transfusion, such as a required question/answer field on type/screen or crossmatch orders. CONCLUSION: Many healthcare systems' transfusion practices for haemoglobinopathy patients are discordant with NHLBI/TIF recommendations. Efforts are needed to increase awareness and implementation of current recommendations among all transfusion services seeing these patients.


Assuntos
Anemia Falciforme , Antígenos de Grupos Sanguíneos , Tipagem e Reações Cruzadas Sanguíneas , Transfusão de Sangue , Conhecimentos, Atitudes e Prática em Saúde , Talassemia , Anemia Falciforme/sangue , Anemia Falciforme/genética , Anemia Falciforme/terapia , Bancos de Sangue , Antígenos de Grupos Sanguíneos/sangue , Antígenos de Grupos Sanguíneos/genética , Estudos Transversais , Humanos , Guias de Prática Clínica como Assunto , Talassemia/sangue , Talassemia/genética , Talassemia/terapia
16.
J Genet Couns ; 28(1): 141-154, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30629758

RESUMO

Members of the public face particular challenges when undergoing reproductive genetic screening. Lack of family history with genetic disease has been identified as a key barrier affecting screening uptake and responses to genetic risk. This study explores this obstacle using beta thalassaemia as a case study. Fifteen in-depth qualitative interviews were conducted exploring the reproductive views and decisions of people at risk of transmitting thalassaemia. Eleven participants had thalassaemia themselves and/or were members of an affected family. Four participants were identified as thalassaemia carriers through genetic screening programmes with no family history. Notable differences were observed between these two groups. For thalassaemic individuals and families, past experience clarified and facilitated their sense of reproductive responsibility, however carriers struggled to relate to, and incorporate the information into their lives. It was witnessing their child becoming symptomatic-rather than receiving a diagnosis or genetic risk information per se that had the most substantial influence on carriers' subsequent views and decisions. Educational resources used to support genetic screening programmes would benefit from an engagement with the experiential accounts of life with genetic disease in order to more effectively bridge the chasm in knowledge and understanding between affected families and the general public, towards whom expansive genetic screening is aimed.


Assuntos
Testes Genéticos , Conhecimentos, Atitudes e Prática em Saúde , Talassemia/diagnóstico , Talassemia/genética , Adulto , Idoso , Tomada de Decisões , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Reino Unido
17.
Transfus Med ; 29(3): 179-184, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29691938

RESUMO

BACKGROUND AND OBJECTIVES: Recently, thalassemia has been introduced as a chronic disease. In spite of prolonging life in thalassemia patients, the quality of their life has not significantly improved. One of the challenges that makes their quality of life poor is alloimmunisation which causes several complications to patients by restricting their options. Some individuals are more susceptible to developing an alloantibody than others. They are categorised as responders and non-responders. Determining responders before the first transfusion allows transfusion services to provide compatible blood and prevent alloimmunisation. The aim of the present study was to determine the relationship between HLA-DRB1*15:03, HLA-DRB1*11 and HLA-DRB1*09:01 alleles and alloimmunisation in Iranian thalassemia patients. MATERIALS AND METHODS: Antibody screening tests were performed by tube method, and HLA-DRB1 genotyping was determined by Sequence-Specific Primers (SSP-PCR) in 59 alloimmunised and 205 non-alloimmunised patients. HLA-DRB1 allele frequencies were compared between alloantibody-positive and -negative groups through the χ2 test. RESULTS: HLA-DRB1*15:03 allele frequency was significantly different between groups (P = 0·000, odds ratio (OR) = 4·193). There was a correlation between HLA-DRB1*11 and anti-K (P = 0·000, OR = 6·643). There was no association between HLA-DRB1*09:01 and alloimmunisation (P = 0·350). CONCLUSIONS: According to our results, detecting HLA-DRB1*15:03 and HLA-DRB1*11 alleles are useful in the pre-transfusion test and could determine responder patients and improve transfusion safety.


Assuntos
Transfusão de Sangue , Cadeias HLA-DRB1 , Imunização , Isoanticorpos/imunologia , Qualidade de Vida , Talassemia , Reação Transfusional , Adulto , Alelos , Formação de Anticorpos , Feminino , Frequência do Gene , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/imunologia , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Talassemia/genética , Talassemia/imunologia , Talassemia/terapia , Reação Transfusional/genética , Reação Transfusional/imunologia
18.
Hemoglobin ; 42(4): 257-263, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30501529

RESUMO

Hemoglobinopathies constitute the most frequent monogenic disorders worldwide and in Greece. In Greece, carrier frequency is estimated at about 8.0%, resulting in a heavy disease burden in the past. Therefore, the implementation of a national prevention program of the disease was an urgent necessity. Moreover, due to migration flow from different geographic areas in the last two decades, the observed spectrum of underlying mutations was expanded, leading to the adaptation of diagnostic approaches. We report the results of the National Thalassaemia Prevention Programme in Northern Greece, over a 15-year period (2001-2015). In total 33,837 healthy at-risk individuals (individuals or couples, 91.0% Greeks) were screened. We have screened 1598 pregnancies in 371 (23.0%) (10.0% non Greeks), of whom both parents carried gene defects and were offered genetic counseling. Seventy-six fetuses (23.0%) were predicted to be affected by severe forms of the disease. Following informed parental choices, 73 of the above pregnancies were terminated. Meanwhile, within the study period, 58 new thalassemic babies (five non Greeks) were referred to the Thalassaemia and Sickle Cell Disease Care Unit of Northern Greece, reflecting mostly parental unawareness, choice or the program failure. Based on the region's population, the birth rate and the prevalence of the disease, the anticipated number of new cases is about 45 annually. According to our data, four thalassemic newborns were registered annually at a stable rate in the last 15 years, reaching a reduction of 90.0% of new affected births. Overall, the National Thalassaemia Prevention Programme effectively decreased the incidence of affected newborns in our region.


Assuntos
Anemia Falciforme/prevenção & controle , Programas de Triagem Diagnóstica , Aconselhamento Genético/normas , Avaliação de Programas e Projetos de Saúde , Talassemia/prevenção & controle , Anemia Falciforme/diagnóstico , Anemia Falciforme/genética , Feminino , Triagem de Portadores Genéticos , Grécia , Humanos , Recém-Nascido , Masculino , Gravidez , Diagnóstico Pré-Natal , Talassemia/diagnóstico , Talassemia/genética , Migrantes
19.
Hematology Am Soc Hematol Educ Program ; 2018(1): 361-370, 2018 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-30504333

RESUMO

Transfusion combined with chelation therapy for severe ß thalassemia syndromes (transfusion-dependent thalassemia [TDT]) has been successful in extending life expectancy, decreasing comorbidities and improving quality of life. However, this puts lifelong demands not only on the patients but also on the health care systems that are tasked with delivering long-term treatment and comprehensive support. Prevention programs and curative approaches are therefore an important part of overall strategy. Curative treatments alter the dynamic of a patient's health care costs, from financial commitment over 50 years, into a potential "one-off" investment. Since the 1980s, this has usually been available only to the 30% or so of young children with matched sibling donors. By improving the safety of matched related donors and haploidentical hematopoietic stem cell transplants, the potential size of the donor pool for curative therapies may be increased. Recent advances in gene therapy demonstrate that even patients lacking a matched donor can be rendered transfusion independent with an autograft of genetically modified autologous stem cells, with a low short-term risk. Noncurative treatments are also of potential value by decreasing use of blood and chelators and decreasing hospital visits. An example is luspatercept, an activin-receptor trap that modifies transforming growth factor-ß signaling, thereby increasing the efficiency of erythropoiesis. This has entered phase 3 clinical trials for TDT and non-TDT and, usefully increases in both Hb and quality of life in non-TDT as well as decreasing transfusion requirements in TDT. Other novel noncurative treatments are entering clinical trials such improvement of erythropoiesis through pharmacological manipulation of hepcidin and iron metabolism.


Assuntos
Terapia Genética/métodos , Transplante de Células-Tronco/métodos , Talassemia/terapia , Doadores não Relacionados , Aloenxertos , Autoenxertos , Humanos , Talassemia/genética , Talassemia/metabolismo
20.
Hemoglobin ; 42(5-6): 310-314, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30558442

RESUMO

Hemoglobin (Hb) synthesis is a complex, well-coordinated process that requires molecular chaperones. These intervene in different steps: regulating epigenetic mechanisms necessary for the adequate expression of the α- and ß-globin clusters, binding the nascent peptides and helping them acquire their native structure, preventing oxidative damage by free globin chains and preventing the cleavage of essential erythroid transcription factors. This study analyzed the distribution of the single nucleotide polymorphism (SNP) rs4296276 in intron 1 of the α-globin chaperone α Hb-stabilizing protein (AHSP) in the Argentinean population. The risk allele was found in thalassemia patients who exhibited more severe phenotypes than expected. Future studies may help establish the role of these chaperones as modifiers in pathological states with globin chain imbalance, such as thalassemia.


Assuntos
Proteínas Sanguíneas/genética , Hemoglobinas/biossíntese , Chaperonas Moleculares/genética , Polimorfismo de Nucleotídeo Único , Alelos , Argentina/epidemiologia , Humanos , Íntrons/genética , Epidemiologia Molecular , Talassemia/genética , alfa-Globinas/genética
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