UMLS:C0019045 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0019045 (hemoglobinopathies)
2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. In a review of methods developed for the identification of fetal malformations, the technique, risks and results of amniocentesis are presented. 2. Large series already published have demonstrated the relative simplicity and feasibility of the procedure as well as current indications for its utilization. These include the detection of chromosomal anomalies, the determination of sex (in certain sex-linked disorders), documentation of enzymatic and metabolic deficiencies, and the demonstration of open lesions of the neural tube by appropriate techniques. 3. Experience with over 500 cases personally tested by the authors entirely confirms the major indications for and benefits of this modern method for the detection and prevention of severe congenital anomalies during early pregnancy. 4. The identification of chromosomal alterations is currently the major objective of the method. Increased risks are associated with pregnancies involving a maternal age of 35 years or older (which account for 1-3% of aneuploidies), the birth of a previous infant with free trisomy 21 (1% recurrence risk) or secondary to a parental chromosome translocation (as much as 10% risk of aneuploidy). Fetal karyotyping for determination of sex, in cases where the mother is a carrier of an X-linked recessive gene (on average, 50% of male offspring will be affected), is an inadequate method of diagnosis to be utilized only until alternative techniques render possible specific diagnosis of the anomalies under consideration (hemophilias A and B, muscular dystrophy, etc). 5. Several of these techniques are now nearing development through the advent of fetoscopy and advanced ultrasound methodology, and have already been applied to the detection of certain sex-linked disorders and also for diagnosis of hemoglobinopathies (thalassemias, sickel cell anemia) and other conditions requiring the obtaining of fetal blood for diagnosis. Technology allowing direct examination of fetal parts by means of optical instruments is particularly useful in cases where a severe fetal morphologic malformation cannot currently be identified by indirect visualization (ultrasound) or by analysis of cytogenetic or molecular markers. 6. Pathological accumulations of alpha-fetoprotein which are associated with diverse feto-placental abnormalities (particularly open malformations of the neural tube) can be detected in the amniotic fluid and/or maternal blood. In extension of this approach, it is foreseeable that conditions existing prenatally will be diagnosed in a growing number of cases from the study of fetal cells and molecules which can be isolated from the venous blood of pregnant women. This will become feasible as a result of some well-developed techniques which allow separation of fetal from maternal cells and metabolites, and also to some extremely fine analytic techniques, notably examination of the DNA itself by means of restriction enzymes.
...
PMID:[Prenatal diagnosis. Review, personal and prospective studies]. 8 63

Circulating erythropoietic precursors in normal men and patients with hemoglobinopathies were characterized in culture. Blood mononuclear cells harvested with a modification of the Ficoll-Isopaque technique were cultured in methylcellulose for 14 days. The majority of erythropoietic colonies consisted of several subcolonies assuming the morphology of erythropoietic "bursts" described in murine marrow cultures. Time course studied of colony formation from marrow and blood nucleated cells confirmed that the circulating erythropoietic precursors represented only early stages of development. Peak sedimentation velocity of the circulating precursors analyzed using a Staput apparatus averaged 5.31 mm/hr and corresponded with that of the early erythropoietic precursors in human marrow. One ml of blood yielded an average of 153 colonies in normal men and 785 colonies in patients with hemoglobinopathies. No correlation was observed between colony formation and reticulocyte indices of individual patients. Examination of the proliferative state of the erythropoietic precursors using high specific activity tritium-labeled thymidine revealed that almost none of the cells in normal men or patients with hemoglobinopathies were in the DNA synthetic phase.
...
PMID:Circulating erythropoietic precursors assessed in culture: characterization in normal men and patients with hemoglobinopathies. 92 59

Alpha thalassemia is the most common single gene mutation worldwide. In Thailand there exists 15-30% alpha-thalassemia carriers distributed throughout the country. DNA analysis by Southern blot hybridization reveals that the two major alpha-thalassemia alleles, alpha-thalassemia 1 and alpha-thalassemia 2 have different extents of alpha-globin gene deletion. In alpha-thalassemia 1, approximately 20 kb of DNA including the two linked alpha 1-and alpha 2-genes are removed and only the alpha-globin gene is intact. Total deletion of the alpha-globin gene cluster is rarely observed. In contrast, only one alpha-globin gene is deleted in alpha-thalassemia 2 of which two types have been detected, one involving a deletion of 4.2 kb of DNA (leftward type, -alpha 4.2) and another of 3.7 kb (rightward type, -alpha 3.7); the latter being more common than the former in Thailand. Compound heterozygosity for alpha-thalassemia 1 and alpha-thalassemia 2 results in HbH disease while homozygosity for alpha-thalassemia 1 leads to Hb Bart's hydrops fetalis, the most severe form of thalassemic disease. Three alpha-thalassemic hemoglobinopathies have been detected in Thailand, two of which produce a remarkable reduction in gene product. Upon interacting with alpha-thalassemia 1 gene they can lead to HbH disease. The most common in this group is Hb Constant Spring which arises from mutation of the termination codon in the alpha 2-gene resulting in an elongation of the alpha-globin chain.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:The molecular basis of alpha-thalassemia in Thailand. 129 97

Polymerase chain reaction (PCR) is a technique to amplify only a specific segment of DNA without using a plasmid or a phage vector. It is a powerful tool for genetic analysis of various diseases including inherited and viral diseases, and is now being applied to clinical diagnosis. Here, presented are several methods using PCR mainly for diagnosis of hemoglobinopathy which we have been engaged in. Some other diseases are also included.
...
PMID:[DNA analysis by polymerase chain reaction]. 132 4

Hb Q-Thailand [alpha 74(EF3)Asp-->His] is often found in Thailand, China, and other Southeast Asian countries. The alpha-Q-Thailand gene is strongly linked to an alpha gene deletion and has important implications in the identification and diagnosis of hemoglobinopathies and thalassemias. The alpha-Q-Thailand mutation was previously mapped to the alpha 1 gene in a study of Chinese patients. In this paper, a Thai patient with Hb Q-Thailand/Hb H disease and his mother were studied at the DNA level, and the gene organization of Hb Q-Thailand in the Thai patient was found to be the same as that of Chinese patients (i.e. the Hb Q-Thailand gene is located on the alpha 1 gene of chromosome #16, while the -4.2 kb or leftward deletion involves the alpha 2 gene). Also, the GAC-->CAC mutation proposed at codon 74, has been confirmed by DNA sequencing and a simple and accurate method for diagnosis of the Hb Q-Thailand variant has been developed based on restriction enzyme analysis. Since the GAC-->CAC mutation generates new cutting sites for both restriction enzymes Apa LI and Hgi AI, polymerase chain reaction amplification of a specific region around codon 74, followed by digestion with these enzymes and agarose gel electrophoresis of the digested products, permits rapid and accurate identification of Hb Q-Thailand.
...
PMID:Hb Q-Thailand [alpha 74(EF3)Asp-->His]: gene organization, molecular structure, and DNA diagnosis. 148 19

This paper summarizes information on the epidemiology and molecular basis of hemoglobinopathies in Yugoslavia. Over the past 25 years, population surveys of more than 28,000 school children from all over the country, except Slovenia, have shown that the average incidence of beta-thalassemia (beta-thal) trait is 1.2%, ranging from 2.9% in the south (Macedonia) to 0.8% in the northwest (Croatia). The frequency of delta beta-thal is 0.2%, while the frequency of the Swiss type of hereditary persistence of fetal hemoglobin (HPFH) is 0.4%. Screening of 6,400 newborns has shown that the frequency of alpha-thal trait is 1.6%. The molecular basis of the different forms of beta-thal among Yugoslavians has been almost completely defined. Over 250 beta-thal chromosomes have been studied, and in over 90% the molecular defect was determined. Eighteen different beta-thal mutations have been detected, three of which (IVS-I-110, G-->A; IVS-I-6, T-->C; IVS-I-1, G-->A) account for more than 70% of all beta-thal chromosomes. Four new mutations [-87 (C-->A); IVS-II-850 (G-->C); initiation codon mutation T-->C; poly A (AATAAA-->AATGAA)] and one new deletion (1605 bp) have been characterized. Molecular analyses of DNA from over 30 unrelated cases with delta beta-thal have shown that this condition is mainly caused by a 13 kb deletion (Sicilian type); in one family a deletion of > 18 to 23 kb (Macedonian type), and in another family a deletion of 148 kb (Yugoslavian type of epsilon gamma delta beta-thal) of the globin gene complex was discovered. Limited studies of alpha-thal in Yugoslavia have shown the following types of molecular defects: approximately 20.5 kb deletion, approximately 17.5 kb deletion, -3.7 kb deletion, 5 nucleotide (nt) deletion, and Hb Icaria. The incidence of abnormal hemoglobins (Hbs) in Yugoslavia is 0.3%. Five different alpha chain variants among 21 families, 15 different beta chain variants among 53 families, one delta chain variant in one family, one variant with a deleted residue in one family, and two types of Hb Lepore among 122 families, have been observed.
...
PMID:Hemoglobinopathies in Yugoslavia: an update. 148 26

This paper reviews the techniques presently available for the prenatal diagnosis of inherited hemoglobinopathies. At the present time, mutations of the globin genes are detected directly in trophoblast DNA, enzymatically amplified by polymerase chain reaction. Known mutations may be defined by restriction endonuclease digestion, non denaturing gradient gel electrophoresis, allele specific oligonucleotide probes or allele specific oligonucleotide primers. Unknown mutations are detected by denaturing gradient gel electrophoresis followed by direct sequencing. Other potentially useful methods for unknown mutations are single strand conformation polymorphism analysis and chemical mismatch cleavage analysis. A potential pitfall for all procedures based on analysis of amplified DNA is the coamplification of maternal sequences. This may be avoided by a careful dissection of maternal decidua from fetal trophoblast, by using an amount of chorionic villi not inferior to 5-10 mg and by reducing the number of amplifying cycles to approximately 20. Monitoring the presence of co-amplified maternal sequences by the analysis of polymorphic sequences is strongly recommended. Future perspectives consist of preimplantation diagnosis by biopsy of the morula or blastula or ova genotyping by analysis of the second polar body.
...
PMID:Prenatal diagnosis of inherited hemoglobinopathies. 162 18

Towards a goal of using recombinant adeno-associated viruses (AAV) for the gene therapy of hemoglobinopathies we had previously constructed plasmid pAV h beta G psi 1, which contained a human beta-globin-encoding cDNA (HBB) downstream from the P40 promoter of AAV2 DNA [Ohi et al., Gene 89 (1990) 279-282]. Transfection of the plasmid into human 293 cells (embryonal kidney cell line) resulted in the expression of HBB at the mRNA level as well as rescue and replication of the recombinant AAV genome (Ohi et al., ibid.). The present study demonstrates that the replicated recombinant DNA was packaged into an intact virion by transcomplementation with pAV2 or the defective helpers, pAV delta Bam or pAVXB. The recombinant virus could be isolated by equilibrium CsCl density gradient, the density of which was about 1.4 g/cm3. The defective helpers are used to produce wild-type AAV-free recombinant AAV. The recombinant AAV were infectious and expressed chimeric mRNAs containing the HBB sequence in virus-infected 293, KB (oral epidermoid carcinoma cell line) and K562 (human erythroleukemia cell line) cells. The importance of the infectivity and expression of the recombinant AAV in hematopoietic cells is discussed in the context of gene therapy of hemoglobinopathies.
...
PMID:Construction and expression of a recombinant adeno-associated virus that harbors a human beta-globin-encoding cDNA. 165 80

Molecular diagnosis of hemoglobin (Hb) Lepore-Boston in the fetus was successfully accomplished using maternal blood as a source for fetal cells in three pregnancies at risk for beta-thalassemia/Hb Lepore disease. Taking advantage of the possibility of amplifying Lepore-specific DNA fragments by polymerase chain reaction and of families in which Hb Lepore was inherited by the paternal side, we demonstrated in two cases and excluded in one case the presence of this hemoglobinopathy in the fetus directly on maternal DNA. The diagnosis was concordant with that obtained by traditional approaches in all three cases. Our results unequivocally show that nucleated fetal cells are present in maternal blood during pregnancy, and demonstrate for the first time that prenatal diagnosis of a genetic disease may be feasible without invasive procedures.
...
PMID:Prenatal diagnosis of fetal hemoglobin Lepore-Boston disease on maternal peripheral blood. 169 93

Human erythroblasts are a logical target for studies of expression of transferred globin genes because high-level expression is a prerequisite for gene therapy of hemoglobinopathies. Early erythroid progenitors (erythroid burst-forming units, BFU-E) are readily available from human peripheral blood and can be cultured to produce erythroblasts. However, conditions for efficient transfer into these normal progenitors have not been previously described. Here we demonstrate efficient transfer of the neomycin resistance gene into human peripheral blood BFU-E using the retrovirus vector, N2. We show that liquid culture of mononuclear cells from peripheral blood for 18-24 h prior to retroviral infection leads to increased transfer efficiency of N2 as determined by G418 resistance, and we are able to detect viral DNA by polymerase chain reaction (PCR) analysis. In addition, a second retrovirus, beta(gamma)-SVX, prepared with a human beta-globin gene containing a gamma-globin second exon to facilitate transcript detection and the 3'-enhancer sequence, was also used to determine whether similar results could be obtained when more than one gene is transferred. Using the beta(gamma)-SVX virus, increased transfer efficiency into BFU-E was similarly found after liquid culture for up to 4 days. Expression of the transferred globin gene was also detected by PCR analysis of cDNA made from erythroblast RNA. The human peripheral blood BFU-E system described should allow determination of sequences required for high-level expression of transferred globin and other erythroid genes.
...
PMID:Retroviral transfer of genes into erythroid progenitors derived from human peripheral blood. 169 73

1 2 3 4 5 6 7 8 9 10 Next >>