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

The thalassaemias are a major group of genetic disorders in Southeast Asia that affect the production of the alpha-globin chain (alpha-thalassaemia) or the beta-globin chain (beta-thalassaemia) of the haemoglobin. As a result of defective globin chain synthesis, individuals with this disorder show varying degrees of anaemia due to ineffective erythropoiesis and haemolysis. The presence of abnormal haemoglobins in thalassaemia patients has enabled the detection of thalassaemia using immunological methods which have certain advantages over the conventional diagnostic methods. This paper reviews the application of various types of antibodies against the different types of haemoglobins used for the detection of thalassaemia. The developed antibodies include the polyclonal antibodies against Hb Bart's and Hb H; monoclonal antibodies (mab) against Hb H, used in a sandwich enzyme-linked immunosorbent assay (ELISA), for detecting carriers of (--SEA/) deletion and deletions involving the complete zeta-alpha-globin gene cluster, such as (--alpha FIL/), (--alpha THAI/) and (--HW/), which are the common deletional alpha-thalassaemias in Southeast Asians; mab against zeta-globin chains used in an immunocytological test, for the detection of adult carriers of (--SEA/) deletion except for (alpha 20.5/), (--alpha FIL/) and (--alpha THAI/) (this simple test is useful in identifying couples at risk of conceiving foetuses afflicted with the Hb Bart's hydrops foetalis syndrome due to homozygous alpha-thalassaemia); mab against Hb A2 and beta- and gamma-globin chains used for the quantitation of Hb A2 in beta-thalassaemia and the diagnosis of beta-thalassaemia major in foetuses respectively; other mabs produced to date include those specific to haemoglobins D-Los Angeles, J-Baltimore, O-Arab and J-Paris-I.
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PMID:Production of monoclonal and polyclonal antibodies against various haemoglobins for the detection of thalassaemias. 877 51

Homozygosity for the South-Asian alpha-thalassemia (--SEA/) deletion is a serious hematological condition that results, in most cases, in intrauterine or postnatal death due to anemia and severe hypoxia of prenatal onset. A relationship between congenital abnormalities and intra-uterine hypoxia has been postulated. However, since homozygosity for the (--SEA/) deletion is most common in underdeveloped countries where detailed autopsies are lacking, the incidence of congenital abnormalities among these babies has not been well delineated. We report on three newborn infants, homozygous for the (--SEA/) deletion, who were born with limb defects. We postulate that this combination is the result of prenatal hypoxia which may affect other fetal body organs. This should be taken into consideration when prenatal treatment of affected fetuses, with intrauterine blood transfusion, is suggested.
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PMID:Limb defects in homozygous alpha-thalassemia: report of three cases. 902 51

The first case of haemoglobin H (HbH) disease in combination with haemoglobin C (HbC) is reported in a man of Surinamese origin. Only haemoglobin A (HbA) and HbC were detected by electrophoresis. The amount of HbC was much less than expected in HbC heterozygotes. The synthesis ratio (beta A+ beta C/alpha) indicated an alpha-thalassaemia defect with two non-functional alpha genes, which did not correlate with the degree of haemolysis and anaemia displayed by the patient. The DNA analysis of the alpha-genes clusters revealed a defect combination -SEA/-alpha 3.7. The haematological data and the physiopathology of this atypical case are compared with the typical HbH disease found in a first cousin of the propositus. Data on the globin chains expression and on the formation of beta A and beta C homotetramers in HbH/HbC disease are presented.
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PMID:Atypical HbH disease in a Surinamese patient resulting from a combination of the -SEA and -alpha 3.7 deletions with HbC heterozygosity. 907 24

alpha-Thalassemia is prevalent among Asian-Americans. Most cases involve deletions of one or more alpha-globin genes. Parents with two-gene cis deletions can have offspring with hemoglobin Bart's hydrops fetalis or hemoglobin H disease. The diversity of deletions poses special challenges to laboratories that offer DNA-based testing for alpha-thalassemia. The purpose of this study was to determine both the frequency of alpha-thalassemia genotypes in a predominantly Asian-American population (n = 78) and the mutation detection rate of a comprehensive Southern blot method. The ethnic composition of the study population was similar to the major Asian-American groups that reside in the United States as a whole. Three mutations (the Southeast Asian type, --SEA; -alpha3.7; and the Filipino type, --FIL) accounted for all mutant alleles present in the Asian-American patients tested for reproductive reasons. The relative frequencies of these three mutations were 62%, 27%, and 11%, respectively. The mutation detection rate was 100%. Laboratories that perform DNA-based alpha-thalassemia testing in populations similar to the one residing in Washington State should use a testing system that allows for the unequivocal identification of the haplotypes detected in the study population, namely --SEA, -alpha3.7, and --FIL.
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PMID:Frequency of deletional alpha-thalassemia genotypes in a predominantly Asian-American population. 912 71

In southeast Asia, the carrier frequency of two-gene alpha-thalassemia deletions is quite high, ranging from 4% to 14% depending on the population. The most common alpha-thalassemia-1 deletion is the so-called southeast Asian deletion (--(SEA)). In addition, a significant proportion of cases involve two other deletions, the Filipino (--(FIL)) and Thai (--(THAI)) deletions. In this report, we identify the deletion breakpoints for the (--(FIL)) and (--(THAI)) deletions, and describe PCR-based protocols for rapid and reliable DNA diagnosis of these deletions.
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PMID:PCR-based diagnosis of the Filipino (--(FIL)) and Thai (--(THAI)) alpha-thalassemia-1 deletions. 1060 70

We describe a sensitive, reliable and reproducible method, based on three multiplex PCR assays, for the rapid detection of seven common alpha-thalassaemia deletions and one alpha-globin gene triplication. The new assay detects the alpha0 deletions - -SEA, - (alpha)20.5, - -MED, - -FIL and - -THAI in the first multiplex PCR, the second multiplex detects the -alpha3.7 deletion and alphaalphaalphaanti3.7 variant, the third multiplex detects the -alpha4.2 deletion. This simple multiplex method should greatly facilitate the genetic screening and molecular diagnosis of these determinants in populations where alpha-thalassaemias are prevalent.
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PMID:Rapid detection of alpha-thalassaemia deletions and alpha-globin gene triplication by multiplex polymerase chain reactions. 1069 58

Alpha-thalassemia has been estimated to account for over 60% of hydrops fetalis cases in Taiwan. The most common genotypic lesion found in alpha-thalassemia-1 cases in Taiwan is deletion of a large segment of the alpha-globin gene cluster, termed the Southeast Asian-type deletion (-SEA/; further referred to as SEA-type deletion). Seven chorionic villus samples (CVS) from pregnancies of couples both heterozygous for SEA-type deletion were studied. Non-radioactive Southern-blot hybridization using the dig-alkaline phosphatase detection system was developed to fulfill this purpose. The results were compared with corresponding polymerase chain reaction (PCR) data to elucidate the effectiveness of these two protocols in the diagnosis of the SEA-type deletion. The data showed that of the seven CVS, three demonstrated a distinctive band pattern, indicating their homozygous status of SEA-type deletion, whereas two showed heterozygous patterns, and the other two were free of the deletion. Homozygosity of the deletion was confirmed by Southern-blot hybridization performed on DNA samples extracted from the abortus tissue. However, two of the three cases with SEA-type deletion showed heterozygous PCR results. Maternal cell contamination could be responsible for the artifacts in the PCR results, but the influence due to the contamination is minimal in non-radioactive Southern-blot hybridization. We concluded that PCR is suitable for screening of carrier adults with SEA-type deletion, and non-radioactive Southern hybridization is ideal for early prenatal diagnosis of the SEA-type deletion.
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PMID:Non-radioactive Southern hybridization for early diagnosis of alpha-thalassemia with southeast Asian-type deletion in Taiwan. 1118 86

A case of hemoglobin H disease in combination with hemoglobin Constant Spring and a beta-globin chain variant is reported in a 3-yr-old Thai girl. On routine cellulose acetate electrophoresis, one abnormal band in addition to the hemoglobins A, A2, H, Bart's and Constant Spring was detected. The amount of this abnormal band movement towards more anodic to the hemoglobin A was 35.7%. DNA analysis of the alpha-globin gene cluster by polymerase chain reaction (PCR) revealed a combination of defects caused by the SEA-type alpha-thalassemia 1 and the alpha-Constant Spring gene. Analysis of beta-globin gene by PCR and DNA sequencing also detected the heterozygosity for the GGC-GAC mutation at codon 56, leading to a substitution of aspartic acid for glycine resulting in the hemoglobin J Bangkok. The hematologic data of this unusual case of hemoglobin H disease are presented and compared with two compound heterozygotes for hemoglobin J Bangkok and alpha-thalassemia 1 found in the patient's father and grandfather. A simple DNA assay based on an allele-specific PCR for rapid diagnosis of the hemoglobin J Bangkok is also described.
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PMID:Atypical hemoglobin H disease in a Thai patient resulting from a combination of alpha-thalassemia 1 and hemoglobin Constant Spring with hemoglobin J Bangkok heterozygosity. 1142 10

Since HbF and HbA are not found in fetuses with Hb Bart's hydrops fetalis the feasibility of prenatal diagnosis of homozygous alpha-thalassemia 1 by fetal hemoglobin typing was examined. Blood samples were obtained from fetuses at 18 to 22 weeks of gestation by cordocentesis in 32 pregnant women at risk of having a child with homozygous alpha-thalassemia 1 (alpha-thal-1). The samples were analyzed by a PCR-based method for the diagnosis of alpha-thal-1 (SEA type) and the proportion of hemoglobin fractions were determined by automated HPLC. DNA analysis showed that 8 of the 32 fetuses were homozygotes for alpha-thal-1, 17 were heterozygous for alpha-thal-1 (alpha-thal-1 trait), and a normal complement of four a-globin genes was found in 7 cases. The Hb typing in fetuses with homozygous alpha-thal-1 showed a peak of unbound Hb (Hb Bart's and Hb Portland) and no HbF, HbA and HbA The alpha-thal-1 trait chromatograms showed unbound Hb, pre HbF, HbF and HbA peaks. The chromatogram of normal fetuses showed HbF and HbA peaks without HbA2. In these cases the HbA proportion is between 3% and 10% with no apparent differences between the 18h and 22nd week of gestation. As the analysis of fetal Hb types by HPLC is facile and speedy and the results correspond with those obtained by DNA analysis, fetal Hb typing by automated HPLC is a convenient prenatal diagnostic method for homozygous alpha-thal-1. The method is recommended for prenatal diagnosis in populations with a high frequency of alpha-thal-1.
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PMID:Prenatal diagnosis of hemoglobin Bart's hydrops fetalis by HPLC analysis of hemoglobin in fetal blood samples. 1148 83

Haemoglobinopathies including alpha- and beta-thalassaemia are the world's most common class of single gene disorder. Prenatal diagnosis (PND) for beta-thalassaemia has been proven to be an effective strategy for controlling the incidence of new cases and is widely used in several countries where the disease is common. Successful preimplantation genetic diagnosis (PGD) protocols for beta-thalassaemia have been introduced using restriction fragment length polymorphism (RFLP), single-stranded conformation polymorphism (SSCP) and denaturing gradient gel electrophoresis (DGGE). However, contamination and allele dropout (ADO) remain an important concern for all of these strategies. In the present study two PGD protocols for detecting beta-thalassaemia mutations (codon 41-42 and IVSI-110) and one for alpha-thalassaemia (SEA mutation) have been designed and tested. These methods contain failsafe mechanisms to reduce the risk of misdiagnosis due to ADO or contamination and utilise multiplex fluorescent PCR (F-PCR). Interestingly, amplification efficiency and ADO were significantly affected by the choice of DNA polymerase and the freshness of the single cells used. The close similarity between the DNA sequences of beta-globin and delta-globin was also found to be an important issue that necessitated careful design of primers for the beta-globin gene.
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PMID:Preimplantation genetic diagnostic protocols for alpha- and beta-thalassaemias using multiplex fluorescent PCR. 1155 12


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