[Thalassemia among Japanese. Report of beta-thalassemia minor in a Japanese family and literature review of reported cases of thalassemia in Japan].
Explore the source record for details and available documents.
Adult↗
SEARCH · Search PubMed
Results for “THALASSEMIA”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
mRNA expression of iron regulatory genes in beta-thalassemia intermedia and beta-thalassemia major mouse models.
beta-Thalassemia is an inherited anemia in which synthesis of the hemoglobin beta-chain is decreased. The excess unmatched alpha-globin chains accumulate in the growing erythroid precursors, causing their premature death (ineffective erythropoiesis). Clinical features of beta-thalassemia include variably severe anemia and iron accumulation due to increased intestinal iron absorption. The most anemic patients require regular blood transfusions, which exacerbate their iron overload and result in damage to vital organs. The hepatic peptide hepcidin, a key regulator of iron metabolism in mammals, was recently found to be low in the urine of beta-thalassemia patients, compared with healthy controls, despite their iron overload. In our work, we measured by RQ-PCR the liver mRNA expression of hepcidin and other iron regulatory genes in beta-thalassemia major mouse model (C57Bl/6 Hbb(th3/th3)), and compared it with beta-thalassemia intermedia mouse model (C57Bl/6 Hbb(th3/+)) and control mice. We found decreased expression of hepcidin and TfR2 and increased expression of TfR1 and NGAL in the beta-thalassemia mouse models, compared with the control mice. Significant down-regulation of hepcidin expression in beta-thalassemia major, despite iron overload, might explain the increased iron absorption typically observed in thalassemia.
Acute-Phase Proteins↗
Thalassemia intermedia caused by heterozygosity for both beta-thalassemia and hemoglobin Saki [beta 14 (A11) Leu replaced by Pro].
The syndrome thalassemia intermedia can be the clinical expression of heterozygosity for different tyes of thalassemia, beta-thalassemia and hereditary persistence of fetal hemoglobin, beta-thalassemia and Hb-Lepore, and in blacks it may even represent a true beta-thalassemia homozygote. This report describes thalassemia intermedia in a white male due to beta-thalassemia and an unstable hemoglobin. Chain-synthesis studies showed an excess of alpha-chain production over beta-chain production in the propositus and his mother but balanced chain synthesis in the clinically normal father, who is heterozygous for the unstable hemoglobin. The unstable hemoglobin was found to be beta14 (A11) Leu leads to Pro, which has previously been described in a clinically normal African woman, and named Hb-Saki. This hemoglobin is not distinguishable from Hb-A on routine electrophoresis at alkaline or acid pH and tests for unstable hemoglobins are necessary for its detection. The increasing list of such hemoglobin variants and previous cases of heterozygosity for beta-thalassemia and unstable hemoglobins are reviewed.
Adolescent↗
Antenatal screening and fetal diagnosis of beta-thalassemia in a Chinese population: prevalence of the beta-thalassemia trait in the Guangzhou area of China.
In this paper beta-globin gene mutations were detected in 452 beta-thalassemia carriers from 13462 unselected individuals (6731 pregnant women and their husbands) who were screened for the beta-thalassemia trait in the Guangzhou area of China. The incidence of beta-thalassemia was calculated as 3.36%. This is higher than found in previous studies performed in southern China. Using reverse dot blot analysis, we found 11 types of mutations and identified the mutations in 446 (98.7%) of the 452 cases. Direct sequencing was carried out on the 6 unknown alleles, and a novel amber mutation in a beta 0-thalassemia gene (beta 37TGG --> TAG) was found in one of them. Thus, the prevalence and spectrum of beta-thalassemia mutations were obtained for this region. Twelve couples were detected at risk for thalassemia, and prenatal diagnosis was carried out in 11 of them. This is the largest number of Chinese subjects studied by DNA analysis to date and is the first report on the prospective diagnostic trial for beta-thalassemia in a Chinese population. In addition, we have performed 80 prenatal diagnoses based on screening for beta-thalassemia retrospectively.
Amino Acid Sequence↗
Beta-thalassemia intermedia from southern Iran: IVS-II-1 (G-->A) is the prevalent thalassemia intermedia allele.
The preliminary results of a pilot study are reported, intended as an initiation of a research plan, focused on the prevention of beta-thalassemia in Iran. The aims of this study are: (i) to improve the knowledge of the molecular background of beta-thalassemia intermedia in Southern Iran; (ii) to verify the role of the -158 (G)gamma (C-->T) (Xmn I) polymorphism as a modulating factor in thalassemia intermedia; (iii) to test the validity of the multiplex and single mutation specific amplification refractory mutation system in analyzing the molecular defects causing beta-thalassemia in multiethnic populations; and (iv) to develop suitable strategies for the application of prevention protocols in Iran. To accomplish the task we have selected 87 beta-thalassemia intermedia patients and adapted the DNA methodology to detect the following 11 frequent mutations in Iran: codon 5 (-CT); frameshift codons (FSC) 8/9 (+G); codon 30 (G-->C); IVS-I-1 (G-->A); IVS-I-5 (G-->C); IVS-I-6 (T-->C); IVS-I-110 (G-->A); codons 36/37 (-T); codon 44 (-C); IVS-II-1 (G-->A); IVS-II-745 (C-->G). Because of the multiethnicity of the population we have also included the Indian IVS-I (25 bp deletion) and the Mediterranean IVS-I-130 (G-->C) and codon 39 (C-->T) mutations. Forty-eight patients were randomly studied for the Xmn I polymorphism together with 50 healthy volunteers as a control group. The molecular analysis conducted in Iran, identified only 31% of the alleles that were presumed to be thalassemic, revealing either a strategic or a technical insufficiency of the chosen method. However, the mutations with the highest prevalence in the country (IVS-II-1, IVS-I-110, IVS-I-1 and FSC 8/9) were found. As expected the IVS-II-1 defect, being the most frequent in south Iran, was present at the highest rate (24%). The Xmn I polymorphism was found in association with this prevalent mutation and was detected in the homozygous state in 87.5% of the patients homozygous for the IVS-II-1 (G-->A) mutation. The overall positivity for Xmn I was found in 40.6% of the thalassemic alleles vs. 14% in the non-thalassemic, confirming the hypothesis of an older event, antecedent to the IVS-II-1 mutation. In trying to assess a more suitable molecular detection method we intend to continue this study in collaboration with the European centers involved, applying more effective technologies and better defining the molecular spectrum of beta-thalassemia in the sub-populations. We also intend to verify the effect of alpha-thalassemia in the genotype/phenotype correlation of beta-thalassemia intermedia.
Case-Control Studies↗
Interaction between HBS-beta-o-thalassemia and alpha-thalassemia.
We have defined the clinical and laboratory characteristics of a group of patients with HbS-beta o-thalassemia plus alpha-thalassemia, by analysis of erythrocyte indices, hemoglobin A2 and F levels, globin biosynthesis studies and alpha-globin gene mapping. Patients with HbS-beta o + alpha-thalassemia closely resembled individuals with HbS-beta o-thalassemia except for balanced globin synthesis ratios and a lower HbF level. The frequency of painful crises, leg ulceration, aseptic necrosis of bone and acute chest syndrome was similar in HbS-beta o + alpha-thalassemia patients and controls with sickle cell anemia (HbSS), HbSS-alpha-thalassemia and HbS-beta o-thalassemia. These findings are consistent with previous work which failed to show a reduction in the vaso-occlusive severity of sickle cell disease by the coexistence of alpha-thalassemia.
Adolescent↗
beta Thalassemia associated with increased HB F production. Evidence for the existence of a heterocellular hereditary persistence of fetal hemoglobin (HPFH) determinant linked to beta thalassemia in a southern Italian population.
A family has been observed in which a beta thalassemia determinant is inherited over three generations together with high Hb F level (8-12%) and increased number of fetal-hemoglobin-containing-cells (F-cells). The values of red cell indices and globin chain synthesis ratios, yet typical of beta thalassemia, were significantly shifted to the normal values when compared with those of typical beta thalassemia heterozygotes belonging to the same family group. The occurrence in these individuals of a heterocellular hereditary persistence of fetal hemoglobin (HPFH) determinant and its linkage relationship with the beta thalassemia is discussed. In the third generation two adult individuals were beta thalassemia homozygotes having inherited a beta thalassemia determinant from one parent and a beta thalassemia together with the HPFH determinant from the other. They showed an extremely mild clinical condition, and 11-12 g/dl of mainly Hb F without having ever required blood transfusions. Virtually all the red cells were F-cells in both subjects. The importance of the coexistence of HPFH determinants capable of increasing the size of the F-cell population in patients affected by homozygous thalassemia is discussed, considering the sensible benefit which derives from enhanced Hb F production in this syndrome.
Adolescent↗
Beta-thalassemia, HB S-beta-thalassemia and sickle cell anemia among Tunisians.
We analyzed the mutations present in 19 patients with beta-thalassemia major, in 11 patients with Hb S-beta-thalassemia, and the beta S haplotypes of 34 patients with sickle cell anemia. The study included 84 relatives. Dot-blot analysis of amplified DNA with various specific oligonucleotide probes identified 11 different known beta-thalassemia mutations and frameshifts; a new frameshift at codons 25/26 (+T) was detected through sequencing of amplified DNA. The common beta-thalassemia mutations at codon 39 (C----T) and at IVS-I-110 (G----A) were also most prevalent among the Tunisian patients, while the milder T----C mutation at IVS-I-6 was not found. All mutations cause a beta 0-thalassemia or a severe beta + -thalassemia [T----A at -30; IVS-I-5 (G----A); IVS-I-110 (G----A)] which explains the need for regular blood transfusions in the thalassemia major and S-beta-thalassemia patients. Nearly all sickle cell anemia patients carried the beta S mutation on a chromosome with haplotype 19 (or Benin) and all had severe anemia with sickling complications. Identification of the beta S haplotype was through dot-blot analysis with oligonucleotide probes that detect mutations in the G gamma and A gamma promoter sequences, specific for this haplotype.
Adolescent↗
[Phenotyping and genotyping studies in a family with the compound heterozygosity for a deletional delta beta-thalassemia and a beta-thalassemia].
OBJECTIVE: To investigate the relationship between genotype and phenotype of a deletional delta beta-thalassemia and explore an approach to rapid prenatal diagnosis for compound heterozygotes of this defect and a beta-thalassemia. METHODS: A total of ten members in a Chinese family who had a 5-year-old propositus with thalassemia major and requested prenatal diagnosis for the second pregnancy were investigated. For genotyping analysis, the deletional delta beta-thalassemia was characterized by gap-PCR method and beta-thalassemia mutations were defined by reverse dot blot(RDB). For phenotyping analysis, hematological data including the RBC indices, quantification of HbF and HbA2 by Hb electrophoresis and the ratio of globin chain Ggamma/(Ggamma+Agamma) analyzed by capillary electrophoresis (CE) were obtained. RESULTS: The propositus inherited her mother's delta beta-thalassemia gene mutation and her father's CD41-42(-CTTT) frameshift mutation. Of nine members in this family screened for this type of deletion, four were positive and the phenotype could be explained satisfactorily by genotype. The results of prenatal diagnosis showed that the fetus was normal and had no beta-globin gene defects in both chromosomes. CONCLUSION: This is the first time to have performed prenatal diagnosis in Chinese family at-risk of compound heterozygotes for beta-thalassemia and delta beta-thalassemia in mailand China. The strategy to analyze the disease presented here may be a valuable reference to the similar problem.
Adolescent↗
[Genetic, biochemical, pathogenetic and laboratory aspects of thalassemia. Heterozygote thalassemia in Alghero].
After reviewing the most recent genetic, biochemic, pathogenetic and laboratory aspects of thalassemia, the Authors refer to a statistical survey of the population of Alghero regarding the thalassemia heterozygote. In order to arrive at the "microcytosis" condition, a study of the average corpuscle volume is recommended as a screening standard. For this purpose, and for technical and economical reasons, automatic continuous flows apparatus are most suitable such as the Technicon SMA 7/A. After emphasizing the difficulty that the laboratory often encounters in diagnosing a heterozygote condition, the Authors report a thalassemic taint of 7.18% in Alghero, with a prevalence of the beta-thalassemia so called 1st type. They refer to the not rare occurrence of anaemia, in association with sideropenia and thalassemia and confirms the possible disappearance of the erythrocytary thalassemia characteristics when, together with the thalassemia there is a deficiency of G-6-PDH. The study carried out by the Authors does not reveal any proven case of alpha-thalassemia, thus confirming what other research workers have established on the rarity of this thalassemia variant in our zone, but not excluding that this apparent rarity could be attributed to an inadequacy in the present means of research.
DNA↗
[Beta-thalassemia mutations and single nucleotide polymorphism at -158 of Ggamma-globin gene associated with altered levels of Hb F in beta-thalassemia heterozygotes].
OBJECTIVE: To investigate the relationship of beta-thalassemia mutations and the single nucleotide polymorphism(SNP) at position -158 of (G)Gamma-globin gene to the altered levels of fetal hemoglobin(Hb F) of beta-thalassemia heterozygotes. METHODS: Hb F was quantitated by alkali denaturation; beta-thalassemia mutations were determined by PCR-allelic specific oligonucleotide(PCR-ASO). The SNP at -158 was analyzed by amplification of (G)Gamma gene promoter fragments from the DNA, followed by Xmn I restriction enzyme digestion. RESULTS: Among 63 cases with beta-thalassemia trait, 15 had Hb F levels above 2% (2.06%-10.44%). Six beta-thalassemia mutations were observed in this study, namely CD41/42(-TTCT), CD17(A-->T), nt28 (A-->G), CD71/72(+A), IVS-II-654(C-->T) and IVS-I-1(G-->T). There was no difference in the incidence of beta-thalassemia heterozygotes of CD41/42, CD17, CD71/72 and IVS-II-654 between 15 cases with Hb F>/=2% and 48 cases with Hb F<2%. Ten (15.9%) heterozygotes of (G)Gamma-158(C-->T)were detected among 63 cases, and 8 of them (53.33%) belonged to the group of Hb F>/=2% while the remaining 2 cases (4.17%) were in the group of Hb F<2%. CONCLUSION: beta-thalassemia mutations of CD41/42, CD17, CD71/72, IVS-II-654 had no influence on Hb F levels, but (G)Gamma-158(C-->T) had a strong association with moderately increased Hb F levels in beta-thalassemia heterozygotes in the Guangxi area of China.
Adult↗
Beta-thalassemia with exceptionally high hemoglobin A2. Differential expression of the delta-globin gene in the presence of beta-thalassemia.
Hemoglobin A2 levels in normal adults are rarely greater than 3.5%. In patients heterozygous for beta-thalassemia, they average about 5% but do not usually exceed 7%. We studied a family in which four patients with heterozygous beta-thalassemia had HbA2 levels of 8.4% to 11.2%. Globin biosynthesis studies and restriction endonuclease mapping of the alpha-globin loci showed homozygous or heterozygous alpha-thalassemia-2 as well as beta-thalassemia in some family members. The delta- and beta-globin genes were examined by using the restriction enzymes Eco RI, Pvu II, and Xba I, which cut both within and outside the coding portions of the delta- and beta-loci. Only the expected delta- and beta-globin gene containing fragments were present, excluding a crossover event producing a fusion gene that would code for delta-globin but possibly be under the regulatory influence of nucleotide sequences that control the expression of the beta-gene. This kindred provides evidence that in the presence of beta-thalassemia, expression of the delta-gene, beyond that commonly seen, is possible. This could be a direct result of the gene defect producing beta-thalassemia or be due to differences in the delta-globin gene linked to this beta-thalassemia gene. The interactions of alpha- and beta-thalassemia may alter tetramer assembly and increase HbA2 levels; however, this possibility seems less likely.
Base Composition↗
Erythrocyte osmotic fragility test for screening of alpha-thalassemia-1 and beta-thalassemia trait in pregnancy.
OBJECTIVES: To evaluate the sensitivity and specificity of osmotic fragility test (OFT) as a screening test in predicting the severe thalassemia trait (alpha-thalassemia-1 & beta-thalassemia). METHODS: A descriptive analysis and diagnostic test of non-anemic pregnant women attending antenatal care clinic, Maharaj Nakorn Chiang Mai, during April, and July 2002 was made. Blood samples were collected from 446 singleton pregnancies with no obvious medical complication such as iron deficiency anemia. OFT was performed in the same day, using 0.45% glycerin saline solution and the cut-off value of less than 60% was used for an abnormal test. Quantitative HbA2 test and PCR (SEA type) were done as a gold standard to confirm the diagnosis of beta-thalassemia trait and alpha-thalassemia-1 trait, respectively. RESULTS: The main outcome measures were sensitivity, specificity, positive and negative predictive value of OFT. If the OFT cut-off value of less than 60% was considered positive, the test had a sensitivity, specificity, positive and negative predictive value of 97.6%, 72.9%, 33.6%, and 99.5%, respectively. CONCLUSION: OFT has high sensitivity in detection of alpha-thalassemia-1 trait or beta-thalassemia trait and due to its simplicity with very low cost it may, therefore, be considered as a screening test in a wide population.
Adult↗
Coinheritance of alpha-thalassemia-1 and hemoglobin E/beta zero-thalassemia: practical implications for neonatal screening and genetic counseling.
Hemoglobin E (HbE), alpha-thalassemia, and beta-thalassemia are common among Southeast Asians and often occur in compound heterozygous states that complicate neonatal screening. We describe a kindred with alpha-thalassemia-1, HbE, and beta zero-thalassemia. The proband had HbE/beta zero-thalassemia, with severe anemia and failure to thrive. His father also had HbE/beta zero-thalassemia but had coinherited alpha-thalassemia-1 and was free of symptoms.
Adult↗
[Detection of alpha-thalassemia 1 gene among 142 beta-thalassemia gene carriers].
OBJECTIVE: To investigate the coincidental rate of double heterozygous state of beta-thalassemia and alpha-thalassemia 1 in Guangdong area. METHODS: One handred and forty-two DNA samples with beta-thalassemia trait were amplified by polymerase chain reaction(PCR) to detect alpha-thalassemia 1 gene. The positive cases were further detected by mutant primer PCR or by reverse dot blot hybridization (ASO/RDB) to confirm their beta-thalassmia mutations. RESULTS: Thirteen cases (9.15%) were identified to combine with alpha-thalassemia 1 gene. The mutant loci of beta-globin gene in these cases were that 5 were in CD 41-42 (-TCTT), 3 in IVS-2-654(C-->T), 2 in CD 17 (A-->T) and 3 in CD 71-72 (+A), CD 43(G-->T) and -28 (A-->G), respectively. CONCLUSIONS: The occurrence of this dual heterozygotes among beta-thalassemia trait is relatively frequent and it should be paid much attention to in genetic counselling and prenatal diagnosis of thalassemia in this area.
Adult↗
Detection of alpha-thalassemia in beta-thalassemia carriers and prevention of Hb Bart's hydrops fetalis through prenatal screening.
The aim of this study was to detect alpha-thalassemia in beta-thalassemia carriers during prenatal screening. During a 12-year prenatal screening program, a total of 158 couples (3.2%) were diagnosed to be the discordant alpha- and beta-thalassemia carriers. Of the 158 beta-thalassemia partners, seven (4.4%) were found to have co-inheritance of alpha0-thalassemia, and three (1.9%) found to have co-inheritance of alpha(+)-thalassemia. Three pregnancies affected with Hb Bart's hydrops fetalis were terminated in the 158 couples. The results showed that molecular analysis must be used for accurate diagnosis of double heterozygotes in couples presumed to be discordant for alpha- and beta-thalassemia on hematologic testing.
Abortion, Eugenic↗
Alpha-thalassemia carrier identification by DNA analysis in the screening for thalassemia.
Differentiation between heterozygous alpha-thalassemia and several phenotypically resembling alleles at the beta-globin gene cluster such as coinherited delta- and beta-thalassemia or gammadelta beta-thalassemia is a critical step in genetic counseling. In this paper we report our experience in the identification of the alpha-thalassemia carrier state using polymerase chain reaction (PCR)-based methods, and the feasibility and simplification of screening for thalassemia using this approach. Alpha-globin genotype was determined by PCR-based method in 526 adult subjects with reduced mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), normal hemoglobin A2 and F, and normal serum iron. To verify the reliability of the protocol used, in 68 of these subjects we performed globin chain synthesis analysis and in 101 we determined alpha-globin genotype by Southern blot analysis. Five hundred twenty-one (99%) of 526 subjects examined were identified as carriers of one or two alpha-thalassemia alleles. The identification of the alpha-thalassemia carrier state may be fast and accurate by PCR-based method, avoiding other cumbersome and expensive methods such as globin chain synthesis and Southern blot analysis.
Adult↗
Non-anemic homozygous beta(o) thalassemia in an African-American family: association of high fetal hemoglobin levels with beta thalassemia alleles.
We have studied a four-generation (23 subjects) African-American family with beta(o) thalassemia and high fetal hemoglobin (HbF) levels. The beta(o) thalassemia in this family is due to the splicing site mutation, beta IVS2+1G-->A, that leads to aberrant mRNA processing and the absence of beta globin. Two members of this family are homozygous for beta(o) thalassemia and are non-anemic. All family members who are heterozygous for the beta IVS2+1G-->A mutation have elevated HbF, with the exception of two individuals who also have severe alpha-globin chain deficiency. We excluded linkage with the hereditary persistence of fetal hemoglobin loci on chromosomes 6 and X. We also excluded the presence of all previously described determinants in the beta globin gene cluster associated with elevated HbF production. One thalassemia allele is in the Cameroon-like (HS2)/Benin-like beta globin gene cluster haplotype, and the other is in the Senegal-like (HS2)/Benin-like beta globin gene cluster haplotype. We speculate that in the homozygotes, those erythroid cells that express low to absent levels of gamma globin are selectively destroyed. In contrast, in the heterozygotes, the presence of the normal beta globin allele would ameliorate the globin chain imbalance and thus allow survival of erythroid cells that express the abnormal transcript, leading to a typical beta(o) thalassemia phenotype. Thus, the heterocellular gamma globin expression together with in vivo preferential survival of HbF-containing erythroid cells ameliorates Cooley's anemia in the beta(o) thalassemia homozygotes. It remains to be determined what sequences linked to each thalassemia allele and what trans-acting factors contribute to high HbF levels.
Adult↗