Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the Mediterranean area, 50% of the beta thalassaemia mutations abolish or create a restriction endonuclease site in the beta globin gene. This study describes a new procedure for prenatal detection of these beta thalassaemia defects based on the direct visualisation, on an ethidium bromide stained polyacrylamide gel, of the discrete DNA fragments produced by restriction endonuclease digestion of fetal DNA, enzymatically amplified using the DNA polymerase from the thermophilus bacterium Thermus aquaticus. We applied this procedure to the Sardinian population to detect the nonsense mutation at codon 39 and the frameshift at codon 6 of the beta globin gene; these are the most frequent beta thalassaemia mutations in this population, accounting for 95% and 2.2% of the beta thalassaemia chromosomes. The main advantages of this procedure are simplicity (no radioactivity), sensitivity (0.2 microgram of DNA), and rapidity (12 hours). The very small amount of fetal material required makes amniotic fluid cell culture unnecessary and may decrease the fetal loss rate associated with trophoblast sampling. By circumventing the use of radioactive and non-radioactive probes, the spread of this technology to the high risk areas will be facilitated.
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PMID:Prenatal diagnosis of beta thalassaemia based on restriction endonuclease analysis of amplified fetal DNA. 273 98

First-trimester prenatal diagnosis by DNA analysis was carried out for seven pregnancies at risk for homozygous alpha 0-thalassaemia. Transabdominal placental biopsy was carried out at 10-12 weeks' gestation. The presence of alpha-globin genes in the fetal DNA was determined by restriction endonuclease mapping and hybridization with cloned alpha-globin probe. Homozygous alpha 0-thalassaemia was detected in two fetuses and the pregnancies were interrupted. Alpha 0-thalassaemia in both cases was confirmed by electrophoresis of the umbilical cord blood where only haemoglobin Bart's was detected. The remaining five fetuses were diagnosed as normal or as possessing alpha-thalassaemia-1 trait and the pregnancies are being carried to term. The use of DNA analysis in prenatal diagnosis of fetuses at risk for homozygous alpha 0-thalassaemia enables detection of the haemoglobinopathy at 10 weeks' gestation.
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PMID:Prenatal diagnosis of homozygous alpha 0-thalassaemia by direct DNA analysis of chorionic villi in Singapore. 276 39

The inheritance of alpha-thalassemia is determined by restriction endonuclease mapping in the members of two Chinese families with history of Hb H disease. One family carries the South East Asia (SEA) deletion in alpha-thalassemia-1 determinant and the nondeletion mutation in alpha-thalassemia-2 determinant. The other family carries the SEA deletion in alpha-thalassemia-1 determinant and the leftward deletion in alpha-thalassemia-2 determinant. Direct analysis of the genetic defects by gene mapping technique is the most reliable method for detecting minor forms of alpha-thalassemia and provides valuable information for genetic conseling in affected families.
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PMID:Structural analysis of the alpha-globin gene cluster in two Chinese families with alpha-thalassemias. 280 75

We have determined the molecular characteristics of alpha-thalassemia in 12 HbH subjects from Taiwan by restriction endonuclease mapping with alpha- and zeta-specific probes. We have found four types of defects in the alpha-thalassemia-2 genetic determinant: -alpha 3.7 type I; -alpha 4.2; alpha CS alpha; and alpha alpha T. All HbH subjects carried the --SEA genotype in the alpha-thalassemia-1 determinant. At least two different subtypes of --SEA genotype were observed in this study.
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PMID:The molecular basis of HbH disease in Taiwan. 282 23

Restriction endonuclease mapping analyses were made of DNA from a few members of a Macedonian family with hematological characteristics of delta beta-thalassemia, ie, microcytosis, normal HbA2 levels, and elevated levels of HbF (7% to 14%) with G gamma (average 40.5%) and A gamma T chains (average 59.5%). A large deletion of 18 to 23 kb was present with a 5' breakpoint within a 670-bp segment of DNA between the HpaI and NcoI restriction sites 5' to the delta globin gene, and a 3' breakpoint between the BamHI and HpaI restriction sites located some 9 to 13 kb 3' to the beta globin gene. This deletion is different from those present in other types of G gamma A gamma(delta beta)zero-thalassemia. The similarity of the hematological expression of these delta beta-thalassemic conditions which have somewhat comparable 5' breakpoints supports the idea that an important fetal hemoglobin-controlling region lies between the psi beta and delta globin genes.
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PMID:The 18- to 23-kb deletion of the Macedonian delta beta-thalassemia includes the entire delta and beta globin genes. 287 56

DNA from members of 2 Thai families with conditions considered to be delta beta-thalassaemia were studied by using restriction endonuclease DNA mapping. The propositus in family A is a double heterozygote for beta-thalassaemia and delta beta-thalassaemia. DNA analysis reveals a deletion of the beta-globin gene cluster starting at the area between the Sac I and Eco RI sites near the 3' end of the G gamma-gene and extending through the A gamma-, delta- and beta-genes to an unknown extent downstream. In family B, the propositus is delta beta-thalassaemia/Hb E. Deletion of the beta-globin gene cluster begins in the large intervening sequence of the A gamma-gene and removes both delta- and beta-genes downstream.
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PMID:Different molecular defects of G gamma (A gamma delta beta)o-thalassaemia in Thailand. 288 16

A study of the molecular pathology of beta thalassaemia in the Asian Indian immigrant population in the U.K. included 37 patients with thalassaemia major and 14 with thalassaemia intermedia. Using a combination of oligonucleotide probe hybridization and restriction endonuclease analysis the mutations in 100/102 (98%) of the beta thalassaemia genes were characterized. Nine different types were found, of which six are associated with beta zero, one with severe beta+ and two with mild beta+ thalassaemia. Comparison of the beta-globin gene cluster haplotypes, alpha globin genotypes and beta gene mutations of the thalassaemia major group with the thalassaemia intermedia group suggests that the co-inheritance of a high Hb F determinant associated with the - + - + + 5' beta haplotype and the inheritance of a mild beta-thalassaemia mutation are the major ameliorating factors of disease severity in Asian Indians. In comparison with other population groups. beta thalassaemia in Asian Indians is not associated with one or two predominant mutations. Despite this, prenatal diagnosis by direct detection is possible in the majority of families by restriction analysis and a limited number of oligonucleotide probes since the majority of severely affected individuals are homozygous for a single mutation. The characterization of these mutations should be useful for the planning of prenatal diagnosis programmes for beta thalassaemia in other Asian Indian communities.
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PMID:The molecular basis of thalassaemia major and thalassaemia intermedia in Asian Indians: application to prenatal diagnosis. 290 65

Using DNA dot-blot hybridization, restriction endonuclease gene mapping with oligonucleotide probes, restriction fragment length polymorphism linkage analysis, and hybridization, prenatal diagnosis was performed for 32 pregnancies at risk for alpha-thalassemia and for 10 pregnancies at risk for beta-thalassemia. The DNA samples were prepared from chorion villi or amniotic fluid cells.
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PMID:Prenatal diagnosis of thalassemia: experiences at the Shanghai Children's Hospital. 290 48

Patients with Hb SC disease were found to have microcytic and hyperchromic red cell indices despite mild reticulocytosis. Iron deficiency anemia was ruled out by the finding of normal serum ferritin levels. In order to determine whether the microcytosis was due to coexistent alpha-thalassemia, restriction endonuclease mapping was performed on genomic DNA extracted from peripheral blood leukocytes. Patients with Hb SC disease had microcytic indices despite the presence of a full complement of four alpha-genes (alpha alpha/alpha alpha), suggesting that the microcytosis may be due to cellular dehydration (or xerocytosis), since the mean corpuscular hemoglobin concentration in Hb SC disease patients was significantly higher than in controls. This possibility was investigated further by the determination of RBC cation content. RBC Na levels were similar in SC and normal red cells. Hb SC RBCs, however, had significantly reduced K levels. These findings show that RBC cation content, and thus cell water, is decreased in Hb SC disease. The decreased RBC K level in the presence of normal cellular Na concentration suggests selective K loss that is not due to inhibition of the Na K pump. Ouabain-insensitive K+ efflux was increased to four times normal in SC cells. Cell dehydration was confirmed by the demonstration of increased high-density RBCs on discontinuous Stractan density gradients and by osmotic gradient ektacytometry. Cellular dehydration and its sequelae were worse in CC erythrocytes and milder in AC cells than in Hb SC red cells. Taken together, these data indicate that in Hb SC disease the RBCs are severely dehydrated and typically microcytic and hyperchromic. Hb SC RBCs seem to be dehydrated due to selective K loss. These findings suggest a functional interrelationship between Hb SC, the red cell membrane, and cation regulation.
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PMID:The xerocytosis of Hb SC disease. 294 42

Gene probes can now be used to detect a variety of mutations that produce single-gene disorders. In present clinical practice, restriction endonuclease analysis is used for the prenatal diagnosis of sickle cell anemia, alpha-thalassemia, and beta-thalassemia. Direct detection of the mutation is possible in alpha-thalassemia, where a deletion has usually occurred, and in sickle cell anemia, where the mutation alters the recognition sequence of the restriction endonuclease, Mst II. Indirect detection of beta-thalassemia is based on using normal variations in DNA (DNA polymorphisms) to track normal and affected beta-globin genes in families. This latter kind of analysis is also useful in detecting the phenylalanine hydroxylase genes affected in phenylketonuria and will often be used in disorders where the mutations are unknown. In cases where the mutation is known, direct analysis by use of oligonucleotide probes is a new and important advance. An example of this type of gene detection in a family with classical hemophilia is presented. In addition, with chorion villus biopsy, detection of these inherited diseases is feasible by the 12th week of pregnancy.
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PMID:Gene probes: application to prenatal and postnatal diagnosis of genetic disease. 299 40


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