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1.
BMC Med Genet ; 21(1): 6, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906886

RESUMO

BACKGROUND: Thalassemia is a group of inherited hemoglobic disorders resulting from defects in the synthesis of one or more of the hemoglobin chains, which is one of the most prevalent inherited disorders in southern China. Only few studies reported the molecular characterization of α- and ß-Thalassemia in Hubei Province in the central of China. METHODS: A total of 4889 clinically suspected cases of thalassemia were analyzed by Gap-PCR, PCR-based reverse dot blot (RDB). RESULTS: 1706 (33.8%) subjects harbored thalassemia mutations, including 539 (11.0%) subjects with α-thalassemia, 1140 (23.3%) subjects with ß-thalassemia mutations, and 25 (0.51%) subjects with both α- and ß-thalassemia mutations. Seven genotypes of α-thalassemia mutations and 29 genotypes of ß-thalassemia mutations were characterized. --SEA/αα (66.05%), -α3.7/αα (24.12%), and -α4.2/αα (3.71%) accounted for 93.88% of the α-thalassemia mutations. ßIVS-II-654/ßN, ßCD41-42/ßN, ßCD17/ßN, ßCD27-28/ßN, ßCD71-72/ßN, ß - 28/ßN, ß - 29/ßN, ßCD43/ßN, ßE/ßN, accounting for 96.40% of all ß-thalassemia genotypes. Furthermore, mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) were sensitive markers for both ß-thalassemia and α-thalassemia with --SEA/αα, but not -α3.7/αα and -α4.2/αα. CONCLUSIONS: Our data indicated great heterogeneity and extensive spectrum of thalassemias in Hubei province of China.


Assuntos
Genética Populacional , Hemoglobinas/genética , Talassemia alfa/genética , Talassemia beta/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China , Feminino , Heterogeneidade Genética , Genótipo , Hemoglobinas/biossíntese , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mutação , Adulto Jovem , Talassemia alfa/epidemiologia , Talassemia beta/sangue , Talassemia beta/epidemiologia
2.
J Clin Pathol ; 73(5): 278-282, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31653757

RESUMO

AIMS: Thalassemia is one of the most prevalent inherited disorders in south China. However, there still has no comprehensive research on molecular characterisation of α-thalassemia and ß-thalassemia in the Quanzhou region of Fujian province, a city with high incidence of thalassemia in Southeast China. METHODS: A total of 11 668 cases were collected in Quanzhou region from January 2013 to June 2019. The deletions of α-thalassemia were detected by Gap-PCR, α-thalassemia and ß-thalassemia mutations were detected by DNA reverse dot blot hybridisation. Rare thalassemia gene testing and DNA sequencing were performed to detect rare and novel thalassemia mutation for suspected rare thalassemia carriers. RESULTS: Among 11 668 subjects, 4796 (41.10%) subjects were diagnosed with thalassemia. 3298 (28.27%) subjects were α-thalassemia carriers, 26 types of α-thalassemia mutations were identified, with the common α-thalassemia genotypes being --SEA/αα (71.47%), -α3.7/αα (17.13%) and -α4.2/αα (3.49%). 1407 (12.06%) subjects were ß-thalassemia carriers, 18 types of ß-thalassemia mutations were identified. The common five genotypes of ß-thalassemia were ßIVS-II-654/ßN (36.53%), ßCD41-42/ßN (30.28%), ßCD17/ßN (17.13%), ßCD26/ßN (5.12%) and ß-28/ßN (4.62%). Additionally, 91 (0.78%) subjects with composite α-thalassemia and ß-thalassemia were identified. Furthermore, 9 α-thalassemia and ß-thalassemia gene mutations (CAP +40-43 (-AAAC), IVS-I-1 (G>T), IVS-I-5 (G>C), SEA-HPFH, CD53 (-T), CD37 (A>G), -90 (C>T), CD3 (T>C), -α6.9) were identified for the first time in the region. Among them, CD53 (-T), CD37 (A>G) and -90 (C>T) mutations were identified for the first time in Fujian province. Moreover, CD3 (T>C), -α6.9 mutations were first identified in Chinese individual. CONCLUSIONS: Quanzhou region of South China has high incidence of thalassemia mutations. In this study, several cases of rare thalassemia mutations have been identified, providing reference for clinical consultation. The completion of this study is of great significance to strengthen the prevention and control of thalassaemia in the Quanzhou region.


Assuntos
Mutação , Talassemia alfa/genética , Talassemia beta/genética , Adolescente , Adulto , China , Feminino , Marcadores Genéticos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Análise de Sequência de DNA , Adulto Jovem , Talassemia alfa/diagnóstico , Talassemia alfa/epidemiologia , Talassemia beta/diagnóstico , Talassemia beta/epidemiologia
3.
J Pak Med Assoc ; 69(7): 959-963, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31308562

RESUMO

OBJECTIVE: To find frequency ofalpha Thalsaemia nhomozygous beta Thalsaemia patients, and to se any difernce infrequency and age ofirst ransfusion and mean haemoglobin concentration. METHODS: The single-centred, escriptive cros-sectional study was conducted athe National Instiute of Blod Disease and Bone Marow Transplantaion, Karchi, from June 1,2012, to May 31, 2013. Patients of homozygous beta halsaemia, diagnosed by polymerase chain reaction, wer tested for coinheritance of alpha Thalsaemia nd foetal haemoglobin XMN1 polymorphism using polymerase chain reaction. SPS 17 was used for dat anlysi. RESULTS: Of the 286 patients, 19(41.6%) wer males, and 9(34.6%) showed coinheritance ofalpha thalsaemia. In the coinheritance group, 50(50%) and 1(1%) patients recived 1-20 and 21-40 times transfusions per year espectively, while inthe non-coinheritance group, the coresponding numbers wer 125(67%) and 27(14.%). Overal, 73(25.%) patients had nevr ben transfused, including 38(13.%) patients inthe alpha Thalsaemia group. XMN1 polymorphism was found in 86(41%) ofthe 208 patients who wer tested and anlysed on this count. CONCLUSIONS: Alpha thalsemia was presnt inmore than one-third homozygous beta halsemia patients.


Assuntos
Talassemia alfa/epidemiologia , Talassemia beta/epidemiologia , Adolescente , Transfusão de Sangue , Criança , Pré-Escolar , Comorbidade , Feminino , Homozigoto , Humanos , Lactente , Recém-Nascido , Masculino , Paquistão/epidemiologia , alfa-Globinas/genética , Talassemia alfa/sangue , Talassemia alfa/genética , Talassemia alfa/terapia , Globinas beta/genética , Talassemia beta/sangue , Talassemia beta/genética , Talassemia beta/terapia
4.
Int J Lab Hematol ; 41(5): 650-656, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31271507

RESUMO

INTRODUCTION: Thalassemias and hemoglobinopathies are the most prevalent inherited anemias detected in South East Asians. These disorders represent not only a clinical health problem but also a socioeconomic problem for this region. Regarding the prevention and control of thalassemias and hemoglobinopathies in the Lao PDR, screening and diagnostic strategies should be strongly considered. The knowledge about the prevalence and molecular genotyping of thalassemias and hemoglobinopathies among the Lao Loum group, which includes the majority of Lao people, is now limited, making the prevention and control of thalassemias difficult. METHODS: This study aimed to determine the prevalence of thalassemia among Lao Loum subjects of reproductive age. Multiplex gap PCR and direct sequencing were used to investigate the mutations of α-globin and ß-globin genes. RESULTS: Thalassemias and hemoglobinopathies were detected in 154 of 354 (43.50%) patients, and 22 different genotypes were identified in this cohort. Remarkably, high frequencies of hemoglobin E, α0 -thalassemia (--SEA ), and α+ -thalassemia (-α3.7 ) were noted. A variety of hematologic features was observed, including co-inheritance of heterozygous HbE and heterozygous α-thalassemia, which was associated with significantly lower levels of MCV and MCH values than those observed in typical HbE heterozygotes. Female participants who were heterozygous for ß0 or co-inheritance of heterozygous ßE with heterozygous α-thalassemia exhibited mild anemia. CONCLUSION: Our data show that thalassemias and hemoglobinopathies have become health problems imposing a serious burden in the Lao PDR. Prevention programs aimed at decreasing the incidence of severe thalassemia diseases should be designed and initiated.


Assuntos
Hemoglobina E/genética , Hemoglobinopatias/genética , Mutação , alfa-Globinas/genética , Talassemia alfa/genética , Talassemia beta/genética , Adolescente , Feminino , Frequência do Gene , Testes Genéticos/métodos , Genótipo , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/epidemiologia , Humanos , Laos/epidemiologia , Masculino , Prevalência , Adulto Jovem , Talassemia alfa/diagnóstico , Talassemia alfa/epidemiologia , Talassemia beta/diagnóstico , Talassemia beta/epidemiologia
5.
Elife ; 82019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31120421

RESUMO

Severe forms of α-thalassaemia, haemoglobin H disease and haemoglobin Bart's hydrops fetalis, are an important public health concern in Southeast Asia. Yet information on the prevalence, genetic diversity and health burden of α-thalassaemia in the region remains limited. We compiled a geodatabase of α-thalassaemia prevalence and genetic diversity surveys and, using geostatistical modelling methods, generated the first continuous maps of α-thalassaemia mutations in Thailand and sub-national estimates of the number of newborns with severe forms in 2020. We also summarised the current evidence-base for α-thalassaemia prevalence and diversity for the region. We estimate that 3595 (95% credible interval 1,717-6,199) newborns will be born with severe α-thalassaemia in Thailand in 2020, which is considerably higher than previous estimates. Accurate, fine-scale epidemiological data are necessary to guide sustainable national and regional health policies for α-thalassaemia management. Our maps and newborn estimates are an important first step towards this aim. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).


Assuntos
Efeitos Psicossociais da Doença , Topografia Médica , Talassemia alfa/epidemiologia , Variação Genética , Hemoglobinas/genética , Humanos , Mutação , Prevalência , Tailândia/epidemiologia
6.
Pediatr Blood Cancer ; 66(8): e27807, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31094093

RESUMO

BACKGROUND: The Uganda Sickle Surveillance Study provided evidence for a large sickle burden among HIV-exposed infants in Uganda. To date, however, no large scale screening program has been developed for Central or East Africa. METHODS: A 3-year targeted sickle cell screening project in Uganda was designed by the Ministry of Health to (1) determine sickle cell trait and disease prevalence within high-burden districts, (2) document the prevalence among HIV-exposed and nonexposed children, (3) confirm previously suggested HIV comorbidity, and (4) estimate the co-inheritance of known genetic modifiers of sickle cell disease. RESULTS: A total of 163 334 dried blood spot samples collected between April 2015 and March 2018 were analyzed, including 112 352 samples within the HIV Early Infant Diagnosis program. A high burden with >1% sickle cell disease was found within targeted East Central and Mid-Northern districts, in both HIV-exposed and nonexposed children. Based on crude birth-rate data, 236 905 sickle cell trait births and 16 695 sickle cell disease births will occur annually in Uganda. Compared to sickle cell disease without HIV, the odds ratio of having sickle cell disease plus HIV was 0.50 (95% confidence interval = 0.40-0.64, P < .0001). Alpha-thalassemia trait and G6PD deficiency were common with sickle cell disease, but with different geospatial distribution. CONCLUSIONS: High sickle cell burden and potential HIV comorbidity are confirmed in Uganda. Genetic modifiers are common and likely influence laboratory and clinical phenotypes. These prospective data document that targeted sickle cell screening is feasible and effective in Uganda, and support development of district-level comprehensive care programs.


Assuntos
Anemia Falciforme/diagnóstico , Genes Modificadores , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Infecções por HIV/diagnóstico , Programas de Rastreamento/métodos , Talassemia alfa/diagnóstico , Anemia Falciforme/complicações , Anemia Falciforme/epidemiologia , Anemia Falciforme/genética , Pré-Escolar , Comorbidade , Feminino , Seguimentos , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Deficiência de Glucosefosfato Desidrogenase/genética , HIV/genética , HIV/isolamento & purificação , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/genética , Humanos , Lactente , Recém-Nascido , Masculino , Prevalência , Prognóstico , Estudos Prospectivos , Talassemia alfa/complicações , Talassemia alfa/epidemiologia , Talassemia alfa/genética
7.
Biomed Res Int ; 2019: 2080352, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31001551

RESUMO

Unlike the other hemoglobinopathies, few researches have been published concerning α-thalassemia in Morocco. The epidemiological features and the mutation spectrum of this disease are still unknown. This regional newborn screening is the first to study α-thalassemia in the north of Morocco. During the period from January 2015 to December 2016, 1658 newborns umbilical blood samples were investigated. Suspected newborns were screened for α-globin defects using Gap-PCR and Multiplex Ligation-dependent Probe Amplification technique. The prevalence of α-thalassemia, its mutation spectrum, and its allelic frequencies were described for the first time in Morocco. Six different α-globin genetic disorders were detected in 16 neonates. This screening valued the prevalence of α-thalassemia in the studied population at 0.96% and showed the wide mutation spectrum and the heterogeneous geographical distribution of the disease. A high rate of carriers was observed in Laouamra, a rural commune in Larache province. Heterogeneity of α-globin alleles in Morocco explains the high variability of α-thalassemia severity. This diversity reflects the anthropological history of the country. These results would contribute to the prevention of thalassemia in Morocco directing the design of a nationwide screening strategy and awareness campaign.


Assuntos
Alelos , Frequência do Gene , Mutação , alfa-Globinas/genética , Talassemia alfa/epidemiologia , Talassemia alfa/genética , Feminino , Humanos , Recém-Nascido , Masculino , Marrocos/epidemiologia , Prevalência
8.
BMC Res Notes ; 12(1): 134, 2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30867026

RESUMO

OBJECTIVE: The alpha-thalassaemia trait has been associated with protection against severe malaria but its role in Plasmodium falciparum asexual parasite and gametocyte carriage remains unclear. This study examined association between prevalence of α-thalassaemia and P. falciparum asexual stage parasitaemia and gametocytaemia in children, pregnant women and adults, which was part of a bigger study that investigated some key factors that influence gametocyte carriage. RESULTS: Overall prevalence of heterozygous α-thalassaemia trait among all the groups was 39.0%, while 8.2% were homozygous alpha thalassaemia. Asexual parasite prevalence was significantly higher in children (P = 0.008) compared to adults and pregnant women. Of the asexual P. falciparum positive individuals, gametocyte prevalence was 38.5% (15/39) in children, 29.7% (11/37) in pregnant women and 17.4% (4/23) in adults. Heterozygous α-thalassaemic children were less likely to harbour asexual parasites, compared with normal and those deficient (OR = 0.52; 95% CI 0.28-0.97; P = 0.037) under the dominant model. These heterozygous children were also associated with reduced risk of parasitaemia compared to heterozygous adults and pregnant women. Children with heterozygous α-thalassaemia trait had reduced risk of asexual parasite carriage. There was however, no association between α-thalassaemia trait and risk of gametocyte carriage.


Assuntos
Portador Sadio , Malária Falciparum , Parasitemia , Plasmodium falciparum , Complicações Infecciosas na Gravidez , Talassemia alfa , Adolescente , Adulto , Idoso , Portador Sadio/epidemiologia , Portador Sadio/parasitologia , Criança , Pré-Escolar , Feminino , Células Germinativas , Gana/epidemiologia , Humanos , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Masculino , Pessoa de Meia-Idade , Parasitemia/epidemiologia , Parasitemia/parasitologia , Plasmodium falciparum/isolamento & purificação , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/parasitologia , Prevalência , Reprodução Assexuada , Adulto Jovem , Talassemia alfa/epidemiologia , Talassemia alfa/genética
9.
Int J Lab Hematol ; 41(3): 397-403, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30830998

RESUMO

INTRODUCTION: The standard screening method for alpha thalassaemia is the examination of HbH preparation. It is labour intensive and poorly standardized. The development of a rapid strip immunochromatographic test (ICT) for haemoglobin Barts offers a fast, user friendly and cost-effective alternative screening tool. METHOD: A total of 180 subjects with results of the thalassaemia screen and genetic testing were included. Results of the ICT and HbH preparation were correlated with genetic results to determine the performance characteristics of the tests and the effect of mean sample age on results. RESULTS: Of 180 subjects, 111 carried alpha thalassaemia mutations and 69 participants had normal genetic results. The ICT had a sensitivity of 63.06% for all alpha gene mutations and 100% for both heterozygous alpha0 and HbH disease, with a specificity of 91.30%. Examination of HbH preparation had a sensitivity of 34.23% overall, detecting 89% of heterozygous alpha0 and 100% of HbH disease with a specificity of 98.55%. Sample age did not affect overall results. CONCLUSIONS: The ICT is a sensitive screening method for significant alpha mutations and detects the majority of homozygous alpha+ and nondeletional mutations. It demonstrates greater correlation with genetic testing than HbH preparation and could replace HbH preparation in the screening algorithm for alpha thalassaemia.


Assuntos
Imuno-Histoquímica/métodos , Talassemia alfa/diagnóstico , Alelos , Estudos Transversais , Grupos Étnicos , Genótipo , Humanos , Programas de Rastreamento , Mutação , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Análise de Sequência de DNA , alfa-Globinas/genética , Talassemia alfa/sangue , Talassemia alfa/epidemiologia , Talassemia alfa/genética
10.
J Clin Lab Anal ; 33(4): e22845, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30809867

RESUMO

OBJECTIVES: Thalassemia is a highly prevalent monogenic inherited disease in southern China. It is important to collect epidemiological data comprehensively for proper prevention and treatment. METHODS: In this study, blood samples collected from 15 807 residents of Chenzhou were primarily screened by hematological tests. A total of 3973 samples of suspected thalassemia carriers were further characterized by combined next-generation sequencing (NGS) and Gap-PCR. RESULTS: In total, 1704 subjects were diagnosed as thalassemia carriers with a total prevalence rate of 10.78%, including 943 α-thalassemia carriers, 708 ß-thalassemia carriers, and 53 composite α and ß-thalassemia carriers. The prevalence rates of α-thalassemia, ß-thalassemia, and composite α and ß-thalassemia were 5.97%, 4.48%, and 0.34%, respectively. Meanwhile, we characterized 19 α-thalassemia variations and 21 ß-thalassemia variations in thalassemia carriers. Approximately 2.88% of thalassemia carriers would be missed by traditional genetic analysis. In addition, four novel thalassemia mutations and one novel abnormal hemoglobin mutation were identified. CONCLUSIONS: Our data suggest a high prevalence of thalassemia and a diverse spectrum of thalassemia-associated variations in Chenzhou. Also, combined NGS and Gap-PCR is an effective thalassemia screening method. Our findings might be helpful for prevention and treatment of thalassemia in this region.


Assuntos
Talassemia alfa/epidemiologia , Talassemia alfa/genética , Talassemia beta/epidemiologia , Talassemia beta/genética , Adolescente , Adulto , Criança , Pré-Escolar , China/epidemiologia , Feminino , Triagem de Portadores Genéticos , Hemoglobinas Anormais/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Mutação , Reação em Cadeia da Polimerase/métodos , Adulto Jovem
11.
Lab Med ; 50(2): 168-173, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30295867

RESUMO

BACKGROUND: The genetic background of patients with hemoglobin (Hb) H disease in Taiwan has been investigated; however, the clinical features and treatment outcomes were not reported. OBJECTIVE: To analyze the clinical features and genotypes of patients with HbH who reside in Taiwan. METHODS: We conducted a retrospective analysis of the clinical and molecular characteristics of 38 patients with HbH disease who were undergoing treatment at Kaohsiung Medical University Hospital, Taiwan. RESULTS: Initial Hb levels were lower and the numbers of patients requiring iron-chelation therapy were higher in the nondeletional HbH group than in the deletional HbH group (P <.05). Compared with the healthy population, the patients with HbH disease exhibited short body length, low body weight, and low body mass index (BMI). CONCLUSIONS: Patients with nondeletional HbH disease had lower Hb levels and a higher requirement for splenectomy and iron-chelation therapy than did those with deletional HbH disease. Also, growth status was compromised in patients with HbH disease.


Assuntos
Talassemia alfa , Adolescente , Adulto , Peso Corporal/fisiologia , Criança , Pré-Escolar , Feminino , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Esplenectomia , Taiwan/epidemiologia , Adulto Jovem , Talassemia alfa/complicações , Talassemia alfa/epidemiologia , Talassemia alfa/genética , Talassemia alfa/terapia
12.
J Clin Lab Anal ; 33(2): e22656, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30129219

RESUMO

BACKGROUND: There is paucity of data on the influence of alpha thalassemia on the clinical and laboratory parameters among Nigerian sickle cell anemia (SCA) patients. This study aimed to determine the prevalence of alpha thalassemia and the influence of alpha thalassemia on laboratory parameters and clinical manifestations in a group of young Nigerian SCA patients. METHODS: This was a cross-sectional retrospective study conducted on 100 patients with SCA and 63 controls. The diagnosis of SCA was confirmed by DNA studies. Alpha thalassemia genotyping was performed by multiplex gap-PCR method. Laboratory parameters including complete blood count, hemoglobin quantitation, serum lactate dehydrogenase (LDH), and bilirubin were determined with standard techniques. RESULTS: Alpha thalassemia was found in 41 (41.0%) patients compared to 24 (38.1%) controls (P = 0.744), and all were due to the 3.7 κb α-globin gene deletions. Alpha thalassemia was associated with more frequent bone pain crisis, higher hemoglobin concentration, red blood cell count, and HbA2 level among the patients. On the contrary, patients with alpha thalassemia had lower mean corpuscular volume, mean corpuscular hemoglobin, and white blood cell count (WBC) (P Ë‚ 0.05). There were 6 (6.0%) patients with leg ulcers, and none of them had alpha thalassemia, P = 0.04. CONCLUSION: This study confirms that coexistence of alpha thalassemia with SCA significantly influences both the clinical and laboratory manifestations of young Nigerian SCA patients. The coexistence of this genetic modifier is associated with increased bone pain crisis and protects against sickle leg ulcers among the patients.


Assuntos
Anemia Falciforme , Talassemia alfa , Adolescente , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/epidemiologia , Anemia Falciforme/genética , Contagem de Células Sanguíneas , Criança , Pré-Escolar , Estudos Transversais , Feminino , Frequência do Gene , Hemoglobinas , Humanos , Masculino , Nigéria/epidemiologia , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Adulto Jovem , Talassemia alfa/sangue , Talassemia alfa/epidemiologia , Talassemia alfa/genética
13.
Medicine (Baltimore) ; 97(45): e13034, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30407298

RESUMO

Thalassemia is an inherited autosomal recessive disorder with microcytic hypochromic anemia resulting from reduced or absent synthesis of 1 or more of the globin chains of hemoglobin. This study provided the insight into prevalence and molecular characterization of thalassemia in Hakka population. 14,524 unrelated subjects were included in our study from January 2015 to November 2017. All the subjects were detected by hematological analysis, hemoglobin electrophoresis analysis, and molecular diagnosis (gap-polymerase chain reaction and flow-through hybridization technology). Data analysis was used to compare allele frequencies between the Hakka populations. Seven thousand four hundred twenty-two cases of microcytosis were found. The percentage of microcytosis in Meizhou, Ganzhou, and Heyuan was 50.91% (6738/13,236), 51.27% (445/868), and 56.90% (239/420), respectively. A total of 5516 mutant chromosomes were identified, including 3775 α-thalassemia and 1741 ß-thalassemia. --/αα was the most common α-thalassemia genotype, followed by -α/αα and -α/αα, accounted for 84.92% of α-thalassemia genotypes. Twelve kinds of mutations and 26 genotypes in ß-thalassemia were found. IVS-II-654(C→T), CD41-42(-TCTT), -28(A→G), and CD17(A→T) alleles accounted for 92.65% of these mutations. IVS-II-654/N, CD41-42/N, -28/N, CD17/N genotypes accounted for 91.53% of ß-thalassemia genotypes. 27 fetuses with at-risk pregnancies were subjected to prenatal diagnosis. Five fetuses were Bart's hydrops syndrome and 2 fetuses with ß-thalassemia major. There were some differences in molecular characterization of thalassemia among Hakka people in different areas of southern China. Our results enriched the related information of thalassemia in the region, which provided valuable references for the prevention and control of thalassemia.


Assuntos
Grupos Étnicos/genética , Talassemia/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Feminino , Frequência do Gene , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mutação , Prevalência , Talassemia/epidemiologia , Adulto Jovem , Talassemia alfa/epidemiologia , Talassemia alfa/genética , Talassemia beta/epidemiologia , Talassemia beta/genética
14.
Hemoglobin ; 42(4): 243-246, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30422721

RESUMO

Hemoglobinopathies are the most common monogenic diseases in the world, causing many health problems worldwide. In Egypt, thalassemia is the most common cause of chronic hemolytic anemia and correlated with significant morbidity and mortality. One thousand Egyptian newborns were screened to detect α-thalassemia (α-thal) deletions using polymerase chain reaction (PCR)-based DNA analysis of cord blood samples. Ninety-one cases (9.1%) of the studied samples were proved to have at least one of the α genes deleted and 851 cases (85.1%) were normal by PCR analysis, while 58 samples (5.8%) failed to be amplified so further DNA analysis could not be done. In the studied group with α gene deletions, we found different types including silent carriers with only one α-globin gene deleted (3.1%), α-thal trait with two α-globin genes deleted (4.2%), Hb H disease with three α-globin genes deleted (1.8%) and no cases carrying Hb Bart's disease with loss of four α-globin genes. We determined the deletional spectrum of α-thal, which might be used in the future for molecular investigations of the disease in susceptible patients in our population.


Assuntos
Talassemia alfa/epidemiologia , Anemia Hemolítica/etiologia , Doença Crônica , Egito , Feminino , Genótipo , Humanos , Recém-Nascido , Masculino , Programas de Rastreamento/métodos , Prevalência , Análise de Sequência de DNA , Deleção de Sequência , Talassemia alfa/genética
15.
Thromb Res ; 172: 61-66, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30384036

RESUMO

BACKGROUND: Thalassemia is characterized by a hypercoagulable state in which the protein C (PC) pathway controls thrombosis. We investigated changes in PC, protein S (PS), antithrombin III (AT III) and soluble endothelial protein C receptor (sEPCR) in thalassemia. METHODS: A group of 129 patients with ß-thalassemia major (ß-TM), ß-thalassemia intermedia (ß-TI), α-thalassemia intermedia (α-TI) and combined α-/ß-thalassemia (α + ß-thal) were compared with 32 gender- and age-matched controls. PC, PS, AT III, sEPCR, thrombin-antithrombin complex (TAT), and intercellular adhesion molecule1 (ICAM-1) antigens were measured by enzyme-linked immunosorbent assay. PC, AT III, and PS activity were assayed by substrate chromatography and a prothrombin time (PT)-based free protein S assay. RESULTS: PC deficiency was seen in 95.3% of the patients and PS deficiency was seen in 77.5%. Concomitant reductions in PC and AT III antigen and activity were observed in ß-TM, ß-TI, and α-TI than in controls (p < 0.005). PC activity was lower in ß-TM than in α-TI (p = 0.004). PS antigen was elevated in ß-TM (p = 0.011) and sEPCR was elevated in α-TI (p = 0.018). Nonsplenectomized patients had lower PC (p = 0.001) and PS (p = 0.006) and higher sEPCR (p = 0.021) than postsplenectomy patients. Transfusion dependent thalassemia (TDT) patients had lower PC levels (p < 0.005) than those with nontransfusion dependent thalassemia (NTDT). ICAM-1 was increased in patient subgroups (p < 0.001), especially those with splenectomies (p = 0.009), and TAT was increased in all patient subgroups compared with controls (p < 0.001) except for α + ß-thal. CONCLUSIONS: Deficiencies of anticoagulant proteins and elevated sEPCR contributed to chronic hypercoagulability in these thalassemia patients of Chinese origin. Splenectomy alleviated these alterations in this patient cohort with the median duration since splenectomy of two years. Blood transfusion was not ideal for avoiding thrombosis.


Assuntos
Antitrombina III/análise , Coagulação Sanguínea , Receptor de Proteína C Endotelial/sangue , Proteína C/análise , Talassemia alfa/sangue , Talassemia beta/sangue , Adolescente , Adulto , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Trombose/sangue , Trombose/epidemiologia , Adulto Jovem , Talassemia alfa/epidemiologia , Talassemia beta/epidemiologia
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(5): 1453-1458, 2018 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-30295267

RESUMO

OBJECTIVE: To investigate the gene prevalence and spectrum of thalassemia in the women of childbearing age in quanzhou area. METHODS: Venous blood of the women were collected for study, all subjects were registered in each county of quanzhou area by using cluster sampling. Both the mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were used for screening thalassemia.Genotyping of the screened positive samples was performed by gap single polymerase chain reaction (gap-PCR) and reverse dot blot (RDB) hybridization.Unknown positive samples were analyzed with DNA sequencing. RESULTS: Out of all 7 082 samples, Three hundred and eighty four were identified as thalassemia gene carriers with a carrying rate of 5.42 %. The α and ß thalassemia were 3.21% and 2.15% respectively. --SEA /αα was the most common genotype with 68.72 % in mutation types of α thalassemia, In addition gene, 2 cases of --THAI/αα and 1 case of αα/αααanti3.7 were also detected. IVS-Ⅱ-654/N and CD41-42/N were the most common gentypes with 75.00 % in mutation types of ß thalassemia gene, 5 cases were found to be α ß compogite thalassemia. CONCLUSION: The carrying rate of thalassemia gene in quanzhou area is higher, and with the most common gentypes including --SEA /αα、IVSⅡ-654(C→T)/N and CD41-42(-TTCT)/N. The study results are beneficial for the screening of thalassemia in the genetic consultation and the prenatal gene diagnosis.


Assuntos
Talassemia alfa , Talassemia beta , China/epidemiologia , Feminino , Heterozigoto , Humanos , Mutação , Gravidez , Inquéritos e Questionários , Talassemia alfa/epidemiologia , Talassemia beta/epidemiologia
17.
Hemoglobin ; 42(3): 161-165, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-30205725

RESUMO

Krüppel-like factor 1 (KLF1) is a pleiotropic erythroid transcription factor that is a regulator of definitive erythropoiesis. The aim of this study was to detect KLF1 gene variants in α-thalassemia (α-thal) carriers with an increased Hb F level in a Chinese population, and determine the changes of hematological parameters as a result of interactions between KLF1 gene mutations and α-thal. Subjects with α-thal and Hb F levels of ≥1.0% were selected for further investigation. Direct sequencing was used to detect KLF1 gene mutations. Hematological parameters of subjects with α-thal and concomitant KLF1 gene mutations and those with α-thal alone were compared. The KLF1 gene variants were detected in 46 of 275 (16.7%) individuals with α-thal and Hb F levels of ≥1.0%. The detection rate of KLF1 gene mutations rose correspondingly when the Hb F level increased. For α0-thal carriers, significantly lower mean corpuscular volume (MCV) and mean corpuscular hemoglobin (Hb) (MCH) values were observed in KLF1 gene mutation-positive carriers than that in KLF1 gene mutation-free carriers; conversely, significantly higher Hb A2 and Hb F levels were observed in the former condition rather than in the latter condition. The results of this study indicate that KLF1 gene variants are common in Chinese subjects with α-thal and increased Hb F levels, and KLF1 gene mutations decreased the red blood cell (RBC) indices in α-thal carriers as that in normal adults.


Assuntos
Hemoglobina Fetal/análise , Fatores de Transcrição Kruppel-Like/genética , Talassemia alfa/genética , Grupo com Ancestrais do Continente Asiático/genética , Índices de Eritrócitos , Feminino , Variação Genética , Hemoglobina A2/análise , Heterozigoto , Humanos , Masculino , Mutação , Talassemia alfa/epidemiologia
18.
Transfusion ; 58(12): 2826-2835, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30260477

RESUMO

BACKGROUND: The severe forms of thalassemia are the most common inherited anemias managed with regular blood transfusion therapy. Transfusion policies and complications are critical to quality of life and survival, but there is a lack of standardized care. STUDY DESIGN AND METHODS: A survey of 58 items was completed in 2016 by 11 centers in California, Washington, Oregon, Nevada, and Arizona providing long-term care for thalassemia. The questionnaire addressed demographic information, transfusion practices and complications, and educational needs. RESULTS: The centers followed 717 patients with ß-thalassemia (314, 43.8%) or α-thalassemia (394, 55%). One-third (34.7%) of patients were transfusion-dependent. Indications and goals of transfusion therapy differed between centers. Prestorage leukoreduction was universal, while routine irradiation of units was limited to one site. Red blood cell antigen phenotype was determined before the first transfusion and patients received Rh/Kell-matched units. However, more than half of the transfused patients had received blood at multiple hospitals within or outside the United States. Alloantibodies were seen in 16.9% of transfused group, but management of such patients was variable. Unusual or emerging transfusion-transmitted pathogens were not observed. Multiple educational needs were recognized, with iron overload as the biggest challenge; the approach to iron chelation varied within the group. CONCLUSION: This study identified many patients not included in earlier surveys limited to major national centers, suggesting that the thalassemia population in the United States is vastly underestimated. Lack of evidence-based guidelines is a barrier to optimal care, which should be addressed through regional consortia of thalassemia centers.


Assuntos
Transfusão de Eritrócitos , Isoanticorpos/sangue , Sistema do Grupo Sanguíneo de Kell/sangue , Sistema do Grupo Sanguíneo Rh-Hr/sangue , Inquéritos e Questionários , Talassemia alfa , Talassemia beta , Adulto , Feminino , Humanos , Masculino , Estados Unidos/epidemiologia , Talassemia alfa/sangue , Talassemia alfa/epidemiologia , Talassemia alfa/terapia , Talassemia beta/sangue , Talassemia beta/epidemiologia , Talassemia beta/terapia
19.
Hemoglobin ; 42(2): 117-121, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30032675

RESUMO

Thalassemia is one of the most prevalent inherited disorders in southern China. However, there have been few reports on molecular characterization of α- and ß-thalassemia (α- and ß-thal) in the large Hakka population living in Meizhou, a city with high incidence of thalassemia in China. A total of 11,631 in- and outpatients in the Hakka area were analyzed by DNA-based α- and ß-thal testing. Of all the samples, 4280 mutant chromosomes were detected, accounting in a total of 35.98%, of which 2864 (24.82%) α-thal mutants were detected, 1268 (10.09%) ß-thal mutants were detected, 148 (1.27%) α- and ß-thal mutants were detected. The following mutations - -SEA/αα (Southeast Asian deletion), ßA/ßA; αα/αα, IVS-II-654 (C>T) (HBB: c.316-197C>T)/ßA; αα/αα, codons 41/42 (-TCTT) (HBB: c.126_129delCTTT)/ßA; and -α3.7/αα, ßA/ßA were the most common thalassemia genotypes. The most common thalassemia genotype in the Hakka population in Meizhou was α-thal. In order to reduce the incidence of severe thalassemia in children, a prevention and control strategy should be established based on the distribution data of thalassemia genotyping. Our findings provide a valuable reference for clinical institutions or local governments to reduce the prevalence of thalassemia in the subtropical regions in the world.


Assuntos
Mutação , Talassemia alfa/genética , Talassemia beta/genética , China/epidemiologia , Genótipo , Humanos , Epidemiologia Molecular , Vigilância da População , Prevalência , Talassemia alfa/epidemiologia , Talassemia beta/epidemiologia
20.
Blood Cells Mol Dis ; 71: 11-15, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29409695

RESUMO

Iron deficiency complicates the use of red cell indices to screen for carriers of haemoglobin variants in many populations. In a cross sectional survey of 7526 secondary school students from 25 districts of Sri Lanka, 1963 (26.0%) students had low red cell indices. Iron deficiency, identified by low serum ferritin, was the major identifiable cause occurring in 550/1806 (30.5%) students. Low red cell indices occurred in iron-replete students with alpha-thalassaemia including those with single alpha-globin gene deletions. Anaemia and low red cell indices were also common in beta-thalassaemia trait. An unexpected finding was that low red cell indices occurred in 713 iron-replete students with a normal haemoglobin genotype. It is common practice to prescribe iron supplements to individuals with low red cell indices. Since low red cell indices were a feature of all forms of α thalassaemia and also of iron deficiency, in areas where both conditions are common, such as Sri Lanka, it is imperative to differentiate between the two, to allow targeted administration of iron supplements and avoid the possible deleterious effects of increased iron availability in iron replete individuals with low red cell indices due to other causes such as α thalassaemia.


Assuntos
Anemia/sangue , Anemia/epidemiologia , Índices de Eritrócitos , Hemoglobinas , Ferro/sangue , Adolescente , Adulto , Anemia/etiologia , Anemia Ferropriva/sangue , Anemia Ferropriva/epidemiologia , Biomarcadores , Criança , Estudos Transversais , Feminino , Genótipo , Testes Hematológicos , Hemoglobinas/genética , Hemoglobinas/metabolismo , Humanos , Masculino , Vigilância em Saúde Pública , Sri Lanka , Adulto Jovem , Talassemia alfa/sangue , Talassemia alfa/epidemiologia
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