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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to provide a noninvasive prenatal diagnosis of alpha(0)-Thalassemia (Southeast Asian [SEA] deletion), we have developed a real-time quantitative semi-nested polymerase chain reaction (PCR) method for identifying the fetal alpha(0)-Thalassemia in maternal plasma. Analysis was performed using DNA extracted from 200 muL plasma from 13 pregnant women during 8-20 weeks of gestation who carried fetuses with normal (2), alpha(0)-Thalassemia carrier (8), Hb H disease (1), and homozygous alpha(0)-Thalassemia (Hb Bart's hydrops fetalis (2). The alpha(0)-Thalassemia was detected using a two-step PCR. Plasma DNA was amplified conventionally using alpha(0)-Thalassemia-specific primers and a portion of the first PCR product was subjected to a semi-nested real-time q-PCR using the SYBR green I chemistry for fluorescence detection. Calibration curve for alpha(0)-Thalassemia quantification was prepared by assaying serial dilution of genomic DNA of an alpha(0)-Thalassemia carrier. Differences in the C(T) (threshold cycle) values and calculated concentrations of amplified DNA among normal fetus, alpha(0)-Thalassemia carrier, Hb H disease, and homozygous alpha(0)-Thalassemia were clearly observed, which could help in prenatal prediction of the fetal genotype. This noninvasive prenatal detection of alpha(0)-Thalassemia in maternal plasma should enhance prenatal diagnostic options for this common genetic disorder in routine DNA diagnostic setting.
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PMID:Development and application of a real-time quantitative PCR for prenatal detection of fetal alpha(0)-thalassemia from maternal plasma. 1710 98

Alpha-Thalassemia is one of the most prevalent hemoglobin disorders in the world, in South-East Asians, the --SEA allele is widely found in the HbH disease patients. The purpose of this work is to describe the molecular characteristics of Hemoglobin H disease in three patients from two Mexican families, as well to analyze the DNA sequence of the --SEA allele to determine the precise site of the crossover. The -alpha 3.7 and --SEA alleles were identified using an established long-PCR method modified in our laboratory. The crossover site of --SEA mutation was analyzed by DNA sequencing. The three HbH subjects showed the same genotype -alpha3.7/--SEA. The -alpha3.7 allele has been observed in almost every racial studied group, whereas the --SEA allele is predominant in South-East Asian countries. DNA analysis through the breakpoint sites of the SEA allele in both families showed the 5' breakpoint at the third base of codon 28 in the psi alpha 2 gene and the 3' breakpoint within an Alu-Jo sequence, 1,328 nucleotides upstream of the 3'HVR. Therefore the size of the deletion is 19,303 nucleotides. This is the first report in which the flanking deletion sites of the --SEA mutation have been analyzed in Mexican patients, the 5' and 3' ends of the deletion is well determined.
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PMID:Molecular characterization of the--SEA alpha thalassemia allele in Mexican patients with HbH disease. 1714 43

The majority of a-thalassemia results from the large deletions in a-globin gene cluster, including both or either one of alpha-globin genes (alpha1 and alpha2). Most common a-thalassemia-2 deletions (single gene deletions) are -alpha3.7 and -alpha4.2, and alpha-thalassemia-1 deletions (double gene deletions) are --SEA, --THAI, --FIL, --MED and -(alpha)20.5 Although it is not easy to diagnose these deletions because of the high GC content at this locus and the sequence homology among psi alpha2, psi alpha1, alpha2 and alpha1 genes, these alleles can now be diagnosed by a single tube multiplex gapPCR assay. We showed here two Saudi Arabian patients with a-thalassemia trait who could be determined their gene mutations according to the method of Chong SS et al. (2000). [Case 1: 21-year-old male] GapPCR assay revealed the amplification of only -alpha3.7, whereas PCR of both a-globin genes showed no amplifications. The results indicate case 1 is a homozygote of -alpha3.7(-alpha3.7/-alpha3.7). [Case 2: 31-year-old male] GapPCR assay revealed the amplification of only -alpha3.7, and PCR of both alpha globin genes showed normal amplification. DNA sequencing of the amplified a-globin genes revealed a point mutation in the poly A site of alpha2-globin gene (AATAAA-->AATAAG), which is known as alpha(T-Saudi). Thus, case 2 was confirmed to be a compound heterozygote of -alpha3.7 and alpha(T-Saudia) alpha(-alpha3.7 / alpha(T-Saudi) alpha). This gapPCR assay is a rapid, reliable screening test for common alpha-thalassemia deletions and seems to be useful for the diagnosis of thalassemic patients without an increase of Hb A2 and/or an abnormality of beta-globin gene.
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PMID:[Genetic screening for alpha-thalassemia deletional determinants by GapPCR method]. 1724 Aug 29

Thalassemia is endemic to many regions in southern China. The screening of severe determinants of thalassemia is of critical importance in management and control of thalassemia. We designed a protocol based on microarray technology to screen for a spectrum of alpha/beta-globin gene mutations in the Chinese population. A total of 38 probes were capable of screening 98% of alpha/beta-globin gene mutations in the China population, including 16 mutations of beta-globin [beta(41-42)(-TCTT), IVSII-654(C-->T), beta17(A-->T), -28(A-->G), beta(71-72)(+A), beta(71-72)(+T), HbE26(G-->A), -29(A-->G), beta(27-28)(+C), IVSI-1(G-->T), IVSI-5(G-->C), beta(14-15)(+G), IVSII-5(G-->C), beta41(+T), 37(G-->A), and beta43(G-->T)] and five mutations of alpha/beta[three deletions of -alpha;(3.7), -alpha(4.2), and --(SEA); two nondeletions of alpha(Quong Sze) codon alpha125(T-->C) and alpha(Constant Spring) codon alpha142(T-->C)]. Multiplex PCR products were amplified from human genomic DNA and allowed to hybridize with the oligonucleotide array. alpha/beta-Globin genotypes were assigned by quantitative analysis of the hybridization results. The protocol, standardized by analysis of 100 thalassemia samples with known mutations and 13 recombinant plasmids, was 100% reliable in genotyping all mutant alleles. In subsequent screening of 2,030 Chinese with unknown mutations, the protocol was 100% accurate. This method provides unambiguous detection of complex combinations of heterozygous, compound heterozygous, and homozygous alpha/beta-thalassemia genotypes. The protocol was also flexible, detecting globin gene mutations from different population groups.
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PMID:Molecular analysis of alpha/beta-thalassemia in a southern Chinese population. 1739 96

Thalassemia is one of the most common monogenic disorders in the world. In order to develop a community-based prevention program, we screened 12,900 individuals for alpha- and beta-thalassemia in Baise City, Guangxi, China, with hematological methods and molecular assays. We found that the frequency of carriers in this area for alpha-thalassemia is 15%. Beta-thalassemia carriers comprise 4.8% of the populations. Five mutations account for 98% of alpha-thalassemia [--SEA 46.7%; -alpha/4.2, 23.9%; -alpha/3.7, 21.7%; hemoglobin (Hb) Constant Spring, 6.5%; Hb Quong Sze, 1.1%]. Seven mutations in the beta-globin gene account for 99% of the mutations [codon (CD) 41/42 (-TCTT) (39.4%), CD 17(A-->T) (32%), CD 71/72 (+A) (7.4%), -28 (A-->G) (5.8%), IVS-2-654 (C-->T) (5.8%), CD26 (Hb E) (4%), IVS-1 (G-->A) (3.7%), and CD 43(G-->T) (1.9%)]. Most individuals with alpha-thalassemia major die in the uterus or shortly after birth. Among 106 patients with beta-thalassemia major followed by our clinic, the majority died before 5 years of age. Knowledge surveys about thalassemia were conducted. Our results show a severe lack of knowledge about thalassemia in both medical professionals and in the general populations. This study shows that thalassemia is a very severe public health issue in minority populations in Baise City, China. Identification of the common mutations will allow us to design cost-effective molecular tests. There is an urgent need to educate the general population and the medical community for a successful community-based prevention program.
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PMID:Current status of thalassemia in minority populations in Guangxi, China. 1748 47

This study was aimed to investigate the prevalence and genotype distribution of heterozygotes in beta-thalassemia combining deletional alpha-thalassemia by using molecular detection and haematological methods. Three common deletions of alpha-thalassemia were detected by using gap-PCR. The mutations of beta-thalassemia were identified by using PCR with reverse dot blot hybridization. The routine analysis of blood cells was carried out. The results indicated that 15 cases from the 81 beta-thalassemia traits were found to be the compound heterozygosity for beta-thalassemia and alpha-thalassemia with 9 different types of gene defects with 18.52% detection rate. There were 6 cases (7.41%) of beta-thalassemia heterozygote combining alpha-thalassemia-1 gene (--(SEA)/alphaalpha), 8 cases (9.88%) combining with alpha-thalassemia-2 gene including 6 (7.41%) right ward deletion (-alpha(3.7)/alphaalpha) and 2 (2.47%) left ward deletion (-alpha(4.2)/alphaalpha), and 1 case (1.23%) combining deletional HbH gene (--(SEA)/-alpha(3.7)). No significant differences were found between beta-thalassemia heterozygotes combining deletional alpha-thalassemia and pure beta-thalassemia in all RBC parameters. It is concluded that the incidence of beta-thalassemia heterozygotes combining with deletional alpha-thalassemia is frequent in Wuzhou city. The hematological analysis can not give specificity for diagnosing these dual heterozygotes. Gap-PCR as a routine method for thalassemia screening has the advantages in reducing the possibility of failing to detect the combining heterozygosity for beta-thalassemia and alpha-thalassemia. It is more useful for genetic counselling and prenatal diagnosis of this disease.
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PMID:[Molecular detection and haematological analysis of heterozygotes in beta-thalassemia combining deletional alpha-thalassemia]. 1749 May 53

We report on a Thai female patient who presented with hypochromic microcytic anemia, hepatosplenomegaly, and failure to thrive since 3 years of age. Hematological and hemoglobin (Hb) analysis were consistent with a clinical diagnosis of Hb H disease. However, no abnormal Hb fraction had ever been detected. During the 20 years of follow-up, this patient experienced several episodes of hemolytic crisis, which worsened her anemia, necessitating blood transfusion. Recently, we identified Hb Quong Sze (Hb QS), a highly unstable globin gene mutation affecting codon 125 (CTG-->CCG) of alpha(2) globin gene in trans with the commonest alpha(0) thalassemia (-(SEA)) in the patient. This report highlights the clinical significance of Hb QS in Southeast Asians, as previously almost all of the patients described with this variant were of Chinese origin.
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PMID:Hemoglobin H disease induced by the common SEA deletion and the rare hemoglobin Quong Sze in a Thai female: longitudinal clinical course, molecular characterization, and development of a PCR/RFLP-based detection method. 1750 46

We defined the molecular basis and analyzed hematological phenotype associated with an unusual form of thalassemia intermedia caused by interaction of the hemoglobin Constant Spring (Hb CS), homozygous Hb E and alpha degrees -thalassemia found in two unrelated pregnant Thai women. Both patients had moderate anemia and characteristic of thalassemia intermedia. Hb-HPLC analysis demonstrated in both cases, Hb E and Hb Constant Spring with 3-4% Hb Bart's. Hb F was marginally elevated (3-5%). Both of them were diagnosed hematologically as the Hb CS EE Bart's disease. DNA analysis revealed the homozygosity for Hb E in both cases and identified the Hb CS mutation in trans to the alpha degrees -thalassemia allele with the SEA deletion in one case and with the Thai deletion in another. The appearance of Hb-HPLC peak resembling the Hb CS in peripheral blood of the two cases indicated the ability to form a tetrameric Hb molecule between alpha(CS) and beta(E) chains leading to a hybrid Hb namely the Hb E-CS (alpha2(CS)beta2(E)) with similar characteristics to Hb CS (alpha2(CS)beta2(A)). Hematological data of the patients were presented comparatively with other forms of related disorders in our series including 2 Hb H/Hb EE diseases, 16 homozygous Hb CS with and without Hb E, 14 Hb H diseases and 35 Hb H-CS diseases. Different genotype-phenotype correlations observed in these Thai patients with these disorders are illustrated.
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PMID:Thalassemia intermedia associated with the Hb Constant Spring EE Bart's disease in pregnancy: a molecular and hematological analysis. 1758 14

Antenatal sickle and thalassaemia screening programmes are now established in most high prevalence areas in England. Although screening reliably detects beta-thalassaemia trait, in many cases, results state that alpha-thalassaemia trait cannot be excluded. The detection of couples at risk of a child with hydrops fetalis is one of the aims of the national programme. We, therefore, performed polymerase chain reaction (PCR) for the common alpha-thalassaemia gene deletions to assess the usefulness of this technique in routine screening practice. Between August 2001 and August 2002, of the 5092 women booked at the antenatal clinic, 425 were found to have a mean corpuscular haemoglobin (MCH) <27 pg in the absence of beta-thalassaemia trait; 189 (44.5%) had an MCH <25 pg. All 425 patients underwent PCR analysis for the common deletions: -SEA (South-East Asian), -MED (Mediterranean), -alpha(20.5), -FIL (Filipino), -alpha 3.7 and -alpha 4.2 genotypes. In total, 130 (31%) women were positive for alpha-thalassaemia deletion; 86 (24.7%) were heterozygous for -alpha 3.7, 19 (4.4%) were homozygous for -alpha 3.7, 12 (2.8%) were heterozygous for -alpha 4.2, 1 (0.2%) was homozygous for -alpha 4.2, 11 (2.6%) were heterozygous for -SEA and one (0.2%) was heterozygous for the -MED genotype. Although the detection rate for alpha(+)-thalassaemia was high, a strategy of selective screening using MCH <25 pg and ethnic group (SEA, Middle East or Eastern MED) would have identified all individuals heterozygous for alpha(0)-thalassaemia. Routine molecular screening for all forms of alpha-thalassaemia trait is unjustified in antenatal screening.
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PMID:Is routine molecular screening for common alpha-thalassaemia deletions necessary as part of an antenatal screening programme? 1841 56

Mutations of the human SLC4A1 gene encoding erythroid and kidney isoforms of anion exchanger 1 (AE1, band 3) result in erythrocyte abnormalities or distal renal tubular acidosis (dRTA) and such mutations are observed in Southeast Asia, where hemoglobinopathies are prevalent. Genetic and hematological studies in 18 Thai patients with dRTA have shown that 12 of them (67%) carried SLC4A1 mutations (7 G701D/G701D, 3 SAO/G701D, and 2 G701D/A858D). Of these 12 patients, three had homozygous G701D/G701D and heterozygous Hb E; one compound heterozygous SAO/G701D and heterozygous alpha(+)-thalassemia; and one compound heterozygous G701D/A858D and heterozygous Hb E. Of 6 patients without SLC4A1 mutation, two each carried heterozygous or homozygous Hb E and one of the latter also had Hb H disease (--(SEA)/-alpha(4.2)). The blood smears of patients with homozygous G701D/G701D showed approximately 25% ovalocytes. Strikingly, the patients with coexistence of homozygous G701D/G701D and heterozygous Hb E had 58% ovalocytes. Similarly, the patients who had compound heterozygous SAO/G701D showed 49% ovalocytes, but the patient with coexistence of compound heterozygous SAO/G701D and heterozygous alpha(+)-thalassemia had 70% ovalocytes. Our previous study has shown that under metabolic acidosis, the patients with homozygous G701D/G701D or compound heterozygous SAO/G701D had reticulocytosis, indicating compensated hemolysis. A patient with compound heterozygous SAO/G701D and heterozygous alpha(+)-thalassemia presented with hemolytic anemia and hepatosplenomegaly which was alleviated by alkaline therapy. Taken together, the coexistence of both homozygous or compound heterozygous SLC4A1 mutations and hemoglobinopathy has a combined effect on red cell morphology and degree of hemolytic anemia, which is aggravated by acidosis.
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PMID:Hematological abnormalities in patients with distal renal tubular acidosis and hemoglobinopathies. 1826 5


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