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1.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(8): 841-847, 2021 Aug 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34511175

RESUMO

OBJECTIVES: To investigate the distribution of genotypes of thalassemia in children in Guangxi, China. METHODS: A total of 30 417 children with positive results of thalassemia screening in the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2011 to December 2019 were enrolled. Single-tube multiplex PCR, agarose gel electrophoresis, and reverse dot blot hybridization technique were used for the detection of common α- and ß-thalassemia genes. Gap-PCR or gene sequence analysis was performed for 2 703 children suspected of rare thalassemia. RESULTS: Among the 30 417 children with positive results of thalassemia screening, 23 214 (76.32%) were diagnosed with thalassemia, and the detection rates of α-thalassemia, ß-thalassemia, and α-thalassemia with ß-thalassemia were 47.77%, 23.75%, and 4.80% respectively. A total of 13 types of α-thalassemia alleles (18 480 alleles in total) were detected, mainly --SEA (54.98%), including seven rare alleles, i.e., --THAI (0.43%), HKαα (0.02%), -α30 (0.01%), -α1.0 (0.01%), -α2.4 (0.01%), -α21.9 (0.01%), and HBA2:C272-279 del (0.01%). A total of 17 types of ß-thalassemia alleles (9 168 alleles in total) were detected, mainly CD41-42 (47.79%), followed by CD17 (25.53%), including three rare alleles, i.e., IVS-II-5 (0.02%), IVS-I-2 (0.01%), and Gγ(Aγδß)0 (0.01%). A total of 37 genotypes were detected in 14 531 children with α-thalassemia, among which the most common 6 genotypes were --SEA/αα (52.20%), -α3.7/αα (13.24%), αCSα/αα (7.52%), -α4.2 (6.06%), --SEA/-α3.7 (5.91%), and αWSα/αα (3.41%), accounting for 88.34%. A total of 49 genotypes were detected in 7 223 children with ß-thalassemia, among which the most common 6 genotypes were CD41-42/ßN (45.81%), CD17/ßN (24.30%), IVS-II-654/ßN (7.49%), -28/ßN (5.62%), CD71-72/ßN (4.42%), and CD26/ßN (3.94%), accounting for 91.13%. A total of 137 genotypes were detected in 1 460 children with both α- and ß-thalassemia, mainly --SEA/αα combined with CD41-42/ßN (14.17%) and CD17/ßN (8.35%). A total of 2 050 children were diagnosed with hemoglobin H disease (α0/α+), among whom 134 had ß-thalassemia heterozygote and 12 had Bart hydrops fetalis syndrome (--SEA/--SEA); 355 children were diagnosed with ß-thalassemia double heterozygote, and 128 were diagnosed with ß-thalassemia homozygote, including 93 children with α-thalassemia. CONCLUSIONS: There are diverse gene mutations and rich genotypes of thalassemia among children in Guangxi, and α-thalassemia is more common, with --SEA/αα as the major genotype. There is a high proportion of children with both α- and ß-thalassemia, and there are relatively high incidence rates of ß-thalassemia double heterozygote and homozygote (intermedia and major).


Assuntos
Talassemia alfa , Talassemia beta , Criança , China/epidemiologia , Genótipo , Heterozigoto , Humanos , Mutação , Talassemia alfa/epidemiologia , Talassemia alfa/genética , Talassemia beta/diagnóstico , Talassemia beta/epidemiologia , Talassemia beta/genética
2.
Rinsho Ketsueki ; 62(8): 914-921, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497231

RESUMO

Thalassemia is caused by a reduced production of one globin chain due to a quantitative imbalance between the α-globin and non-α-globin chains that make up the hemoglobin. It is classified into α- and ß-thalassemia and characterized by microcytosis with polycythemia, and a Mentzer index of ≤13 aids in the diagnosis. In the genetic analysis of α-thalassemia, the Southeast Asian type was found to be the most common genetic subtype among Japanese and non-Japanese without a substantial difference. Conversely, the genetic analysis of ß-thalassemia revealed differences in the types and frequencies of mutations between Japanese individuals and foreigners living in Japan, with Japanese-specific mutations such as -31 A→G (TATA box). Acquired α-thalassemia exists in exceptional cases, and cases of myelodysplastic syndrome with acquired Hemoglobin H disease have been reported as α-thalassemia myelodysplastic syndrome. Recent trials using a novel therapeutic agent, luspatercept, for transfusion-dependent ß-thalassemia revealed that luspatercept safely and significantly reduces the transfusion volume.


Assuntos
Talassemia alfa , Talassemia beta , Transfusão de Sangue , Humanos , Japão/epidemiologia , Mutação , Talassemia alfa/diagnóstico , Talassemia alfa/epidemiologia , Talassemia alfa/genética , Talassemia beta/diagnóstico , Talassemia beta/epidemiologia , Talassemia beta/genética
3.
Int J Public Health ; 66: 629338, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335138

RESUMO

Objectives: Newborn screening in the United States and Europe allows early identification of congenital disorders but does not yet exist in most low-resource settings, especially in sub-Saharan Africa. Newborn screening can identify multiple inherited hematological disorders, but feasibility and effectiveness for Africa are not fully determined. Methods: Surplus dried blood spot collected in Central Malawi through the HIV Early Infant Diagnosis surveillance program were repurposed and tested by isoelectric focusing for sickle cell disease and trait. Additional genetic testing identified G6PD deficiency and alpha thalassemia. Results: Testing of 10,529 cards revealed an overall sickle cell trait prevalence of 7.0% (range 3.9-9.7% by district); 10 of 14 infants identified with sickle cell disease (prevalence 0.1%) were located and received care at a specialized clinic. Subsequent testing of 1,329 randomly selected cards identified alpha thalassemia trait in 45.7% of samples, and G6PD deficiency in 20.4% of males and 3.4% of females, with 29.0% of females as heterozygous carriers. Conclusion: Inherited hematological disorders are common in Central Malawi; early identification through newborn screening can improve clinical outcomes and should be supported throughout Africa.


Assuntos
Anemia Falciforme , Doenças Hematológicas , Triagem Neonatal , Anemia Falciforme/diagnóstico , Feminino , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Deficiência de Glucosefosfato Desidrogenase/genética , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/genética , Humanos , Recém-Nascido , Malaui/epidemiologia , Masculino , Estudos Prospectivos , Talassemia alfa/diagnóstico , Talassemia alfa/genética
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1262-1265, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34362513

RESUMO

OBJECTIVE: To explore the differences between hematological phenotypes of patients with different genotypes in gene mutations and deletion α- thalassemia. METHODS: By screening the α- thalassemia gene test results in the First Affiliated Hospital, Sun Yat-Sen University from January 2015 to April 2020, the patients with mutation and deletion α- thalassemia were obtained, then the differences between hematological phenotypes of patients with different genotypes were analyzed. RESULTS: There were 96 patients with mutation combined with deletion α- thalassemia from the results of 24 054 α- thalassemia patients screened out, including 79 patients with non-deletion Hb H disease (αTα/--SEA) and 17 patients with mild α- thalassemia (αTα/-α), the incidence was 0.42%. Except the number of red blood cells (RBC) and mean corpuscular volume (MCV), the hemoglobin (Hb) concentration, hematocrit (Ht), average red blood cell hemoglobin concentration (MCHC), average red blood cell hemoglobin amount (MCH), average red blood cell volume (MCV) of the patients with αTα/--SEA genotype were significantly lower than those with αTα/-α genotype. The Hb of the patients with αCSα/--SEA and αQSα/--SEA genotype was (86±20)g/L and (84±9)g/L, respectirely, which was significantly lower than (114±16) g/L of αWSα/--SEA genotype (P<0.05); The MCHC of patients with αCSα/--SEA and αQSα/--SEA genotype was (278.8±8.5) g/L and (282.1±21.1)g/L, respectirely, which was also significantly lower than (315.4±19.5) g/L of αWSα/--SEA genotype (P<0.05); There was no significant difference between the patients with αCSα/--SEA and αQSα/--SEA genotype in hematological phenotypes. Except MCH and MCV, there was no significant differences between the patients with αWSα/--SEA and αTα/-α genotype in RBC, Hb, and Ht. The result of Hb A2 was (2.3±0.9)% for only 27 patients who performed electrophoretic analysis. There was no significant difference between the patients with αTα/--SEA and αTα/-α genotype in Hb A2, aslo among 3 types of the patients with αTα/--SEA genotype. CONCLUSION: The hematological phenotype changes caused by αWSα/--SEA genotype are similar to those of mild α- thalassemia, and both of them are significantly lighter than those patients with αCSα/--SEA and αQSα/--SEA genotype.


Assuntos
Talassemia alfa , Genótipo , Humanos , Mutação , Fenótipo , Estudos Retrospectivos , Talassemia alfa/genética
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1266-1270, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34362514

RESUMO

OBJECTIVE: To analyze the genotypes and distribution of thalassemia in children in Quanzhou Region so as to provide reference for the prevention and control of thalassemia. METHODS: A total of 1 302 children with suspected thalassemia were collected from January 2014 to April 2020 in Quanzhou Region. The deletional α-thalassemia was detected by Gap-PCR, and DNA reverse dot blot (RDB) hybridization was used to detect α- and ß-thalassemia mutations. RESULTS: In the 1 302 cases, 667 cases were identified as thalassemia carriers, and the positive detection rate was about 51.23%. Among them, 380 cases of α-thalassemia gene were detected, and --SEA/αα was the most common genotype with the composition rate about 69.21%. Forty-two cases were identified as HbH disease, and -α3.7/--SEA was the most common genotype. While, 274 cases were identified as ß-thalassemia, and ßIVS-Ⅱ-654/ßN (35.40%) and ßCD41-42/ßN (33.94%) were the most common genotypes. Seventeen cases of ß-thalassemia major/intermedia were identified, and the most common genotypes were ßIVS-Ⅱ-654/ßIVS-Ⅱ-654 and ßIVS-Ⅱ-654/ßCD17. Meanwhile, 13 cases of α- complex ß- thalassemia were detected. Among them, 1 case of ß-thalassemia gene rare mutation Term CD+32 was firstly detected in Fujian Province, and 1 case of CD14-15 mutation was firstly detected in Quanzhou Region. In addition, 3 cases of abnormal hemoglobin disease were identified, in which 2 cases were Hb Q-Thailand and 1 case was Hb G-Honolulu. CONCLUSION: There are various genotypes of thalassemia in children in Quanzhou Region, and many children with thalassemia major or intermedia. Therefore, further prevention and control of thalassemia need to be strengthened for reducing the birth of thalassemia major or intermedia.


Assuntos
Talassemia alfa , Talassemia beta , Criança , China , Testes Genéticos , Genótipo , Heterozigoto , Humanos , Mutação , Talassemia alfa/genética , Talassemia beta/genética
6.
Int J Hematol ; 114(3): 307-318, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34195938

RESUMO

This study investigated prenatal diagnosis of α-thalassemia and ß-thalassemia in 3049 families in 18 regions of Hainan Province. Molecular diagnosis was performed in 3049 couples with thalassemia in Hainan Province. Genomic DNA was extracted from peripheral blood of the couples and villus, amniotic fluid, or cord blood of fetuses. DNA-based diagnosis was performed using polymerase chain reaction. The most commonly detected mutation for α-thalassemia was- SEA/αα (31.53%), followed by - α4.2/αα (11.15%) and - α3.7/αα (11.02%). The most common mutation for ß-thalassemia was CD41/42 (30.27%), followed by - 28 (2.56%). Prevalence was highest in the coastal regions and lowest in the Wenchang, Lingao, and Ding'an regions. We also found that the most common gene mutations in Han people and other minority groups were not homogeneous. Prenatal diagnosis showed 556 normal fetuses, 116 with α-thalassemia hydrops, and 134 with ß-thalassemia major. Our findings provide important information for clinical genetic counseling regarding prenatal diagnosis for thalassemia major in Hainan Province.


Assuntos
Mutação , alfa-Globinas/genética , Talassemia alfa/epidemiologia , Talassemia alfa/genética , Globinas beta/genética , Talassemia beta/epidemiologia , Talassemia beta/genética , China/epidemiologia , Feminino , Genótipo , Geografia Médica , Heterozigoto , Humanos , Masculino , Gravidez , Prevalência , Talassemia alfa/diagnóstico , Talassemia beta/diagnóstico
7.
Nat Commun ; 12(1): 3806, 2021 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-34155213

RESUMO

Many single nucleotide variants (SNVs) associated with human traits and genetic diseases are thought to alter the activity of existing regulatory elements. Some SNVs may also create entirely new regulatory elements which change gene expression, but the mechanism by which they do so is largely unknown. Here we show that a single base change in an otherwise unremarkable region of the human α-globin cluster creates an entirely new promoter and an associated unidirectional transcript. This SNV downregulates α-globin expression causing α-thalassaemia. Of note, the new promoter lying between the α-globin genes and their associated super-enhancer disrupts their interaction in an orientation-dependent manner. Together these observations show how both the order and orientation of the fundamental elements of the genome determine patterns of gene expression and support the concept that active genes may act to disrupt enhancer-promoter interactions in mammals as in Drosophila. Finally, these findings should prompt others to fully evaluate SNVs lying outside of known regulatory elements as causing changes in gene expression by creating new regulatory elements.


Assuntos
Elementos Facilitadores Genéticos/genética , Mutação com Ganho de Função/genética , Regiões Promotoras Genéticas/genética , Regulação da Expressão Gênica , Humanos , Família Multigênica , Mutação Puntual , Transcrição Genética/genética , alfa-Globinas/genética , Talassemia alfa/genética
8.
Niger J Clin Pract ; 24(6): 874-882, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34121736

RESUMO

Background: Sickle cell disease (SCD) is a monogenic, phenotypically highly variable disease with multisystem pathology. The phenotypic heterogeneity of SCD is attributed to environmental and genetic factors such as fetal hemoglobin and co-inheritance of α-thalassemia. Objectives: To look for different types of α-thalassemia gene mutations among SCD patients and evaluate the influence of the co-inheritance of α-thalassemia on clinical and hematological variables. Methods: This cross-sectional analytical study included 765 SCD patients, and 150 patients (with low mean corpuscular volume (MCV), low mean corpuscular hemoglobin (MCH) and normal serum ferritin levels) were tested for α-thalassemia gene mutations. Multiplex PCR and reverse hybridization and sequencing for both α genes using the Vienna Lab Strip Assay PCR study were performed using conventional PCR technology. Results: Out of 150 patients tested for α-thalassemia gene mutations, 141 patients were found to have one or more of the mutational types, representing 18.4% of all studied SCD patients. The most common mutations found were the -3.7 deletion (76.6%), followed by the -4.2 deletion (12.1%), mutant α2polyA-1 (Saudi type) (9.2%), and --MED double gene deletion (7.8%). Acute painful episodes did not differ significantly in sickle cell anemia (SCA) patients with or without α-thalassemia, although the co-inheritance of α-thalassemia has a protective role against many disease-related complications. However, this role was not observed with other types of SCD. The means of red blood cell count, hemoglobin, and hematocrit were significantly higher, while the MCV, MCH, reticulocyte count, and hemoglobin A2 percentage were significantly lower in patients with α-thalassemia gene mutations than in those without α-thalassemia gene mutations (P < 0.05). Conclusions: The co-inheritance of α-thalassemia and SCA confers protection against many disease-related complications and is associated with improved hematological indices. However, this protection was not noticed in patients with other types of SCD.


Assuntos
Anemia Falciforme , Talassemia alfa , Anemia Falciforme/epidemiologia , Anemia Falciforme/genética , Estudos Transversais , Índices de Eritrócitos , Humanos , Mutação , Talassemia alfa/epidemiologia , Talassemia alfa/genética
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(3): 860-864, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34105484

RESUMO

OBJECTIVE: To analyze the gene defect types and distribution characteristics of α- and ß-thalassemia in Lingui District of Guilin City, Guangxi, so as to provide scientific basis for genetic consultation and prevention measures. METHODS: A total of 6 496 suspected cases for screening the thalassemia during physical examination, premarital examination, pregnancy examination and hospitalization in the Second Affiliated Hospital of Guilin Medical University from May 2016 to October 2019 were analyzed. Gap-PCR, PCR-RDB and DNA sequencing techniques were used to detect the types and constituent ratios of gene defects in α- and ß-thalassemia positive cases. RESULTS: Among 6 496 suspected patients, 1 363 were thalassemia carriers, the total positive rate was 20.98%. There were 677 cases of single-gene deletion and 26 cases of double-gene detetion on the deletional α-thalassemia, 115 cases of non-deletion α-thalassemia mutation and 4 cases of deletion plus mutation. The positive rate of α-thalassemia was 12.66%. There were 11 gene abnormalities for α-thalassemia, of which --SEA/αα (50.36%) was the most common, followed by -α3.7/αα (23.84%); the main α-gene mutation was ααCS (6.93%). There were 514 ß-thalassemia gene carriers, with a positive rate of 7.93%. In 12 types of ß-gene mutations, CD41-42 (-TTCT) (55.64%) was the most common, followed by CD17 (A→T) (20.23%). There were 25 cases of double heterozygous α and ß thalassemia (0.39%), of which -α3.7/ßCD17 (24%) and --SEA/ß41-42 (16%) were numerically dominant. Two of rare thalassemia genotypes were identified by sequencing, which were heterozygous mutations of Chinese Hong Kong type α thalassemia (HKαα/αα or HKαα/-α3.7) and ß gene mutations IVS-I (-2) or codon30 (A→G) ß0, respectively. CONCLUSION: Lingui district of Guilin city is a high incidence area of thalassemia. The mutation rate of α-thalassemia --SEA/αα type deletion is relatively high, followed by that of the right deletion type (-α3.7/αα). CD41-42 (-TTCT) has the highest mutation rate in ß-thalassemia, followed by CD17(A→T). The results of this study provide reference data for the regional screening, diagnosis and treatment of thalassemia and eugenics.


Assuntos
Talassemia alfa , Talassemia beta , China/epidemiologia , Feminino , Genótipo , Heterozigoto , Humanos , Mutação , Gravidez , Talassemia alfa/epidemiologia , Talassemia alfa/genética , Talassemia beta/epidemiologia , Talassemia beta/genética
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(3): 865-868, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34105485

RESUMO

OBJECTIVE: To understand the genotypes and distribution characteristics of thalassemia in Baise, Guangxi Zhuang Autonomous Region, to provide references for the prevention and diagnosis of thalassemia in the region and improve the quality of eugenics. METHODS: 3 482 pregnant women and their spouses from January 2019 to August 2019 in Baise Maternal and Child Health Hospital for prenatal genetic diagnosis were selected, α, ß- thalassemia genes were detected by Gap-PCR, PCR and DNA reverse dot hybridization, cases carrying thalassemia gene were confirmed and statistical analyzed. RESULTS: 2 260 samples (64.90%) carrying thalassemia gene were found, among which 1 459 cases (64.56%) were diagnosed as α- thalassemia, 617 cases (27.30%) as ß- thalassemia, 184 cases (8.14%) as α complex ß- thalassemia. Among 1 459 α- thalassemia genes, --SEA /αα(637 cases, 43.66%), -α3.7 /αα (306 cases, 20.97%), -αCS /αα(143 cases, 9.80%), -α4.2 /αα(124 cases, 8.50%) and -αWS /αα(77 cases, 5.27%) were the most common, while among 617 ß- thalassemia genes, CD17 (229 cases, 37.12%), CD41-42 (213 cases, 34.52%), IVS-I-1 (41 cases, 6.65%), ßE (38 cases, 6.16%) and CD71-72 (34 cases, 5.51%) were the most common. And --SEA /αα/ CD17 (24 cases, 13.04%), -α4.2 /αα/ CD17 (13 cases, 7.07%), -α3.7 /αα/ CD41-42 (12 cases, 6.52% ) and --SEA /αα/ CD41-42 (12 cases, 6.52%) were mainly found in 184 cases of α complex ß - thalassemia. CONCLUSION: Genotyes of thalassemia in Baise, Guangxi Zhuang Autonomous Region are complex and diverse. The prenatal screening and diagnosis of thalassemia in the region should be strengthened in accordance with the characteristics of genetypes in the region, in order to reduce birth defects and improve eugenics quality.


Assuntos
Talassemia alfa , Talassemia beta , Criança , China , Feminino , Genótipo , Humanos , Mutação , Gravidez , Diagnóstico Pré-Natal , Talassemia alfa/diagnóstico , Talassemia alfa/epidemiologia , Talassemia alfa/genética , Talassemia beta/diagnóstico , Talassemia beta/genética
11.
Eur J Med Genet ; 64(8): 104251, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34051360

RESUMO

Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome is caused by a mutation in ATRX, which is essential for proper chromatin remodeling. ATRX dysfunction leads to dysregulation of many genes due to abnormal chromatin remodeling, and causes a multisystem disorder in patients with ATR-X. Because mitochondrial disorders also show multisystem involvement, whether mitochondrial function is affected in patients with ATR-X is of interest. Here, we report a case of a 4-year-old male with a mutation (NM_000489.4: c.736C > T p.Arg246Cys) in ATRX, who showed mitochondrial dysfunction with complex I deficiency. The results from our study suggest that target genes of the ATRX protein may include those responsible for mitochondrial function, and mitochondrial dysfunction may contribute to some ATR-X phenotypes.


Assuntos
Complexo I de Transporte de Elétrons/metabolismo , Retardo Mental Ligado ao Cromossomo X/genética , Proteína Nuclear Ligada ao X/genética , Talassemia alfa/genética , Células Cultivadas , Pré-Escolar , Complexo I de Transporte de Elétrons/genética , Fibroblastos/metabolismo , Humanos , Masculino , Retardo Mental Ligado ao Cromossomo X/patologia , Mutação , Talassemia alfa/patologia
12.
Blood Cells Mol Dis ; 89: 102563, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33798832

RESUMO

Hemoglobin H (Hb H) disease is the most significant health problem of the α-thalassemia syndromes. The Hb disease patients are categorized based on their genotype to deletional and nondeletional, with the latter genotype presents the more severe clinical symptoms. Since telomere length is an indicator of biological aging and health, we hypothesized that telomere length could reflect Hb H disease's severity. In this study, we recruited 48 deletional and 47 nondeletional Hb H disease patients, along with 109 normal controls, for telomere length assessment. The leukocyte telomere length was assessed by monochromatic multiplex real-time PCR and reported as the telomere to single-copy gene (T/S) ratio. When telomere length was adjusted for age, the analysis of covariance between the control and the two Hb H disease groups revealed no significant difference. However, the telomere shortening rate was more rapid in the nondeletional Hb H disease group than those of the control and deletional Hb H disease groups. Gender analysis found that male patients have a significantly lower T/S ratio than females in the nondeletional group but not in the control and deletional groups. In the two disease groups, the T/S ratio was not influenced by ferritin level or transfusion burden but was positively correlated with the absolute reticulocyte count.


Assuntos
Hemoglobina H/genética , Encurtamento do Telômero , Talassemia alfa/genética , Globinas beta/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transfusão de Sangue , Criança , Feminino , Ferritinas/sangue , Deleção de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem , Talassemia alfa/sangue , Talassemia alfa/diagnóstico , Talassemia alfa/terapia
13.
Clin Lab ; 67(4)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33865246

RESUMO

BACKGROUND: Iron deficiency and thalassemia are two commonly encountered microcytic and hypochromic anemias. The primary objective was to find the best discriminant formula between alpha thalassemia and iron deficiency to be used in premarital screening centers. The secondary objective, was to find cutoff values that might differentiate alpha thalassemia, beta thalassemia, and iron deficiency collectively. METHODS: A total of 224 females divided into four groups (normal, alpha thalassemia, beta thalassemia, and iron deficiency) were recruited in this study after carrying out complete blood count, hemoglobin electrophoresis, serum ferritin, and molecular analysis. Based upon the laboratory data, 26 discriminant formulas (DF) were applied to differentiate alpha thalassemia, beta thalassemia, and iron deficiency anemia. Receiver Operating Characteristic (ROC) curve was constructed and sensitivity, specificity, and Youden's index were determined. RESULTS: In this study, Shine and Lal, Ehsani, Telissani, Sirachainan, Hisham, Kandhro 2, and Mantos indexes showed 100% sensitivity, specificity, Youden's index, and 1.00 AUC for differentiating alpha thalassemia from iron deficient group. Formulas that showed best sensitivity and specificity (100%) in the discrimination of beta thalassemia and iron deficiency were Mentzer, Shine & Lal, Sarivastava & Bevington, and Sirachainan index (AUC 1.00). AUC of Mentzer index was lower (0.988 vs. 1.00) in differentiating alpha thalassemia and iron deficiency than beta thalassemia and iron deficiency. CONCLUSIONS: Almost all discriminant formulas can be utilized for the prediction of microcytic anemia in a premarital setup after excluding beta thalassemia; however, further confirmation is mandatory for genetic counselling and iron supplementation. Furthermore, Bordbar, Kerman index I, and Huber-Herklotz index showed the lowest performance in the discrimination of alpha thalassemia and iron deficiency.


Assuntos
Anemia Hipocrômica , Anemia Ferropriva , Talassemia alfa , Talassemia beta , Anemia Ferropriva/diagnóstico , Diagnóstico Diferencial , Índices de Eritrócitos , Feminino , Humanos , Ferro , Talassemia alfa/diagnóstico , Talassemia alfa/genética , Talassemia beta/diagnóstico
14.
Ann Hematol ; 100(6): 1429-1438, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33851260

RESUMO

Thalassemia is a common genetic disorder. We aimed to present thalassemia mutation data that covers a period of 7 years from the Mediterranean region of Turkey by comparing with hemoglobin indices and to contribute to prenatal diagnosis and genetic counseling studies which should be decided very quickly. In this study, in which a retrospective archive was scanned, the cases were first grouped as α and ß thalassemia, and then ß thalassemia mutations were examined in a total of 5 groups as UTR-Pro, Codon, IVS, ß0, and ß+. We have reached the family of the proband that analyzed their Hb indices and genetic mutation. All mutations were statistically compared with Hb indices, HbF, and HbA2. We have identified two new ß thalassemia mutations that have the feature of not being defined previously [HBB:C*62 A>G. (3'UTR+1536 A>G) and HBB:C*1 G>A (3'UTR+1475 G>A)]. The most commonly encountered 23 mutations account for 74.7% of all mutations which is unlike the literature. In the ß thalassemia group, 73 different mutations were detected. The most common ß thalassemia mutation was HBB: c.93-21 G>A (IVS I-110 G>A) with a frequency of 19.72%. A statistically significant difference was found when comparing the mutation groups with Hb indices. We think that it may be useful to evaluate the mutations we have newly identified too together with the Hb indices especially in evaluating the carriers of thalassemia and it will contribute to prenatal diagnosis and genetic counseling studies which should be decided very quickly.


Assuntos
Polimorfismo de Nucleotídeo Único , Talassemia alfa/genética , Globinas beta/genética , Talassemia beta/genética , Regiões 3' não Traduzidas , Adolescente , Adulto , Feminino , Humanos , Masculino , Região do Mediterrâneo/epidemiologia , Mutação , Taxa de Mutação , Mutação Puntual , Estudos Retrospectivos , Turquia/epidemiologia , Adulto Jovem , Talassemia alfa/epidemiologia , Talassemia beta/epidemiologia
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 596-620, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33812437

RESUMO

OBJECTIVE: To detecte the carrying rate, the type and distribution of α-Thalassemia gene mutation in Honghe Prefecture, Yunnan Province, and analyze the differences in average erythrocyte volume (MCV), mean erythrocyte hemoglobin content (MCH) and hemoglobin among different types of α-Thalassemia. METHODS: The DNA samples from small cell hypochromic carriers or anemia patients and women of childbearing age who underwent hematological screening in The First People's Hospital of Honghe State was from 2015 to 2019 were enrolled and analyzed, and the mutation types and frequency of alpha-thalassemia positive rate were diagnosed by PCR reverse dot blot or PCR fluorescence dissolution curve. RESULTS: Among the 1 016 samples, 141(13.88%) of the patients were diagnosed as α-thalassemia. The α-thalassemia was subdivided into 3 types, silent (36.17%), minor (51.77%), and HbH disease (12.06%), and the MCV, MCH and HB levels were detected and showed a obvious decrease trend with significant difference (P < 0.05). The gene mutation types were 9 kinds, the deletion type gene was mainly --SEA (51.06%), followed by -α3.7/αα deletion (29.79%), the α- mutation type gene was mainly αcsα(3.55%). The absence of complex heterozygote was most common, which was 17 cases, accounting for 12.77%, mainly --SEA/-α3.7 (10.64%). The areas were mainly distributed in Mengzi (47.52%), followed by Jinping (17.02%). Ethnic groups were mainly distributed in Han nationality (49.65%), followed by Zhuang (15.60%), Yi (3.48%) and Dai (7.09%). The patients with double heterozygous mutation was slightly higher in Mengzi than that in Jinping County (4.26% vs 3.55%), the Dai (2.13%) showed Zhuang ethnic group (2.13%) had the relatively high incidence except the Hans, and showed the most serious anemia. CONCLUSION: Alpha-thalassemia in Honghe prefecture of Yunnan Province shows complex genetic diversity and significant genetic heterogeneity, and the mainly type of gene mutation is --SEA and --SEA/-α3.7, which is mainly distributed in Han, Zhuang and Dai ethnic groups in Mengzi, Jinping. The anemia index of HbH group is the most obvious, and it is significantly different from other groups.


Assuntos
Talassemia alfa , Talassemia beta , China , Feminino , Genótipo , Heterozigoto , Humanos , Mutação , Talassemia alfa/genética
17.
Genet Test Mol Biomarkers ; 25(3): 247-252, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33734896

RESUMO

Introduction: Alpha- and beta-thalassemia are caused by reduced or absent synthesis of hemoglobin (Hb) subunits α and/or ß. HBA2, HBA1, and HBB mutations are the main cause of thalassemias. The aim of this article is to analyze molecular and hematological features of α- and ß-thal in a cohort of Mexican patients. Methods: One hundred forty-one thalassemia patients were studied. Peripheral blood was collected for blood cell count, electrophoresis, Hb quantification, and molecular testing. Molecular screening was performed by Gap-PCR, ARMS-PCR, Sanger sequencing, and MLPA. Results: Fifty-four patients had α-thal, 75 ß-thal, and 12 patients were complex cases, we observed 13 α- and 18 ß-thal alleles in 43 genotypes, -α3.7/αα and ßCd39C>T/ß were the most frequent. Four α-thal deletions (-Mex4 included HBA2 and HBA1, whereas (αα)Mex5, Mex6 and Mex7 involved MCS-R), a hereditary persistence of fetal hemoglobin-2 like (HPFH-2 like) deletion and six alleles not previously reported in Mexicans (α-59C>Tα, -α4.2, αPlasenciaα, ß-32C>T, ßInitCdA>C and ßFSCd71/72+A) were identified. Conclusion: The observed alleles denote the high heterogeneity and multiple origin admixture of Mexican population. Hematological data are consistent with genotypes, variability in simple carriers, from asymptomatic forms to mild or moderate anemia, was ascertained. We emphasize the importance to consider hematological parameters to establish adequate molecular screening strategies.


Assuntos
Talassemia alfa/genética , Talassemia beta/genética , Alelos , Estudos de Coortes , Feminino , Hemoglobina Fetal/genética , Genótipo , Hemoglobina A Glicada/genética , Hemoglobina A2/genética , Hemoglobinas/genética , Heterozigoto , Humanos , Masculino , México/epidemiologia , Mutação , Talassemia alfa/metabolismo , Globinas beta/genética , Talassemia beta/metabolismo
18.
Clin Biochem ; 92: 77-81, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33675809

RESUMO

OBJECTIVE: To describe a new mutation causing alpha thalassemia and its mechanism of action. DESIGN AND METHODS: The propositus was a 37-year-old man who presented maintained microcytosis without iron deficiency. Molecular characterization was undertaken using automatic sequencing after testing negative for the most frequent α-globin mutations by multiplex PCR followed by reverse-hybridization. RESULTS: The mutation is a single base substitution at codon 65 of the α1 globin gene [α65(E14) Ala>Pro; HBA1: c.196G>C] and leads to the substitution of a proline residue in the E helix. The resulting hemoglobin variant has been named Hb Maruchi. This new variant cannot be separated from Hb A by electrophoretic and chromatographic techniques. CONCLUSIONS: The substitution α65(E14) Ala>Pro; HBA1: c.196G>C causes a α-thalassemia silent associated with a very mild phenotype. The diagnosis of this type of mutation is important because it may cause alpha thalassemia if inherited with other clinically relevant HBA1/HBA2 variants.


Assuntos
Hemoglobinas Anormais/genética , alfa-Globinas/genética , Talassemia alfa , Adulto , Humanos , Masculino , Mutação Puntual , Prolina/genética , Espanha , Talassemia alfa/diagnóstico , Talassemia alfa/genética
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 188-192, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554817

RESUMO

OBJECTIVE: To understand the carrying rate, gene mutation frequency and composition ratio of thalassemia in pregnant women in Suxian and Beihu districts of Chenzhou, Hunan Province. METHODS: Thalassemia gene in 11 212 samples was analyzed by using Next-Generation Sequencing. RESULTS: Among the 11 212 samples, 938 were diagnosed as thalassemia, in which 618 (5.51%) were diagnosed as α-thalassemia, 268 (2.39%) as ß-thalassemia, 29(0.26%)as abnormal hemoglobin and 23 (0.21%) as αß-thalassemia. The gene mutations of --SEA /αα(40.29%) and -α3.7/αα(37.7%) in α-thalassemia were the most common, while for ß- thalassemia, the most commonly gene mutation were ß41-42M/ßN(24.26%) and ß654M/ßN(23.88%). The detection rate of rare type α,ß-thalassemia gene was 0.19%(21/11 212), 0.53%(59/11 212), respectively. CONCLUSION: The carrying rate of thalassemia in pregnant women is 8.37% in Suxian and Beihu districts of Chenzhou city, and the genotypes are complex. Next-Generation Sequencing can detect rare thalassemia genes and new gene mutations effectively.


Assuntos
Hemoglobinas Anormais , Talassemia alfa , Talassemia beta , China , Feminino , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação , Gravidez , Gestantes , Talassemia alfa/genética , Talassemia beta/genética
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 217-220, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554823

RESUMO

OBJECTIVE: To explore the diagnostic value of HBA2 in different types of thalassemia by analyzing the sensitivity and missed diagnosis rate of HBA2 in different types of thalassemia. METHODS: 1 178 couples in the department of women's health of Chongqing maternal and child health hospital were selected for pregnancy examination. Peripheral venous blood was extracted and analyzed for parallel blood routine test, hemoglobin capillary electrophoresis and thalassemia gene detection. RESULTS: A total of 265 cases of thalassemia gene carriers were screened out in 1 178 couples; 91.3% ß0 heterozygous thalassemia and 94.74% ß+ heterozygous thalassemia could be screened out using HBA2 > 3.5% as cut-off value; 30.19% stationary α-thalassemia and 66.07% standard α-thalassemia could be screened out using HBA2 < 2.5% as cut-off value. The rate of missed diagnosis of α-thalassemia and ß-thalassemia was 47% and 1.01% respectively when the blood routine screening is positive. CONCLUSION: HBA2 shows different diagnostic value for different types of α-thalassemia and ß-thalassemia. The sensitivity of HBA2 > 3.5% is higher than that of HBA2 < 2.5%. More attention should be paid to the further screening of patients with normal electrophoresis results when the blood routine screening is positive.


Assuntos
Talassemia alfa , Talassemia beta , Criança , Feminino , Testes Hematológicos , Hemoglobina A2/análise , Humanos , Programas de Rastreamento , Gravidez , Talassemia alfa/diagnóstico , Talassemia alfa/genética , Talassemia beta/diagnóstico
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