Prenatal Diagnosis Of Thalassemia Research Articles

Thalassemia Syndromes: Recent Advances

Laboratory and clinical investigators in the past several years have provided many advancements in the understanding of the thalassemia syndromes and in the care of affected patients. The diversity of genetic defects causing thalassemia has been extensively explored, with major benefits to our knowledge of normal globin gene function and of the consequences of specific mutations. In addition, the use of molecular biology methods in these studies has provided major advances in population genetics, gene transfer, and prenatal diagnosis of thalassemia. In the clinical area, guidelines for transfusion, splenectomy, prevention of postsplenectomy infection, and effective iron chelation have been considerably improved, and bone marrow transplantation is now available as an alternative means of treatment. Despite these advances, a great deal remains to be done in the areas of understanding the developmental regulation of globin gene expression, effective gene transfer, oral chelation therapy, safer blood products, and other important areas that will benefit patients afflicted with thalassemia.

Application of DNA polymorphisms for prenatal diagnosis of beta thalassemia in Chinese.

Forty-seven Chinese suffering from beta thalassemia major and their parents were studied to establish linkage of the beta thal and beta A genes with 11 restriction site polymorphisms. There is marked linkage disequilibrium at the BamH I site 3' to the beta globin gene, such that, in 31% of pregnancies, absence of the site in the fetus can exclude beta thalassemia major. Using four restriction sites (Hinc II psi beta, Ava II beta, Hind III beta, and BamH I beta), prenatal diagnosis is feasible in all families. In 46% of all cases, a definitive diagnosis can be made, and in the remaining cases, a 50% chance of exclusion is possible. Fetal blood globin chain analysis would be required for the failures. Our experience in nine successive beta thalassemia prenatal diagnosis is also reported.

Prenatal diagnosis of thalassemia and of the hemoglobinopathies; a review.

Prenatal diagnosis of thalassemia and of the hemoglobinopathies is now accepted as an effective measure to reduce the impact of these diseases in populations where they occur in high frequencies. The procedure has been carried out on more than 5,000 cases over the past decade. Evaluation of the results shows a significant decrease of the yearly number of affected newborns and reflects a considerable gain in economic and medical resources. Methodology has improved over the years so as to make the procedure safer, faster, and less expensive. Among recent advances, gene mapping on trophoblast DNA (as early as the 9th week of pregnancy) represents a major step which will gradually replace conventional procedures (performed during the 18-20th week of pregnancy) in concerned laboratories.

Prenatal diagnosis of thalassaemia by haemoglobin chromatography on Biorex. An evaluation of the method.

The applicability of the chromatographic separation of haemoglobin F, A and S on Biorex 70 ( Blouquit et al., 1982) for the prenatal diagnosis of thalassaemia and related conditions was evaluated in comparison to the conventional globin chain separation technique. The method proved reliable, inexpensive and rapid and should be considered as a valuable alternative in laboratories carrying out great numbers of tests and those being newly set up for this purpose.

Prenatal diagnosis of thalassaemia and fetal red cell microcytosis.

Prenatal diagnosis of thalassaemia and fetal red cell microcytosis.

HAEMOGLOBIN BART'S HYDROPS FETALIS SYNDROME IN AN INFANT OF GREEK ORIGIN AND PRENATAL DIAGNOSIS OF ALPHA‐THALASSAEMIA

An unusual case of Bart's hydrops fetalis is reported where the patient was born to parents of Greek origin. An exchange transfusion was given. Adult haemoglobin (HbA) was present in addition to HbBart's and HbPortland. A low level of synthesis of alpha-chains was evident. The mother presented again in a subsequent pregnancy for prenatal diagnosis of thalassaemia. The fetus was diagnosed as an alpha-thalassaemia carrier, a diagnosis which was confirmed at birth. The nature of alpha-thalassaemia in the family is discussed.

Application of endonuclease mapping to the analysis and prenatal diagnosis of thalassemias caused by globin-gene deletion.

We applied a recently developed and more direct technic to diagnose thalassemia syndromes associated with deletion of particular globin structural genes and to assess a fetus at risk for one of those conditions, deltabeta-thalassemia. The method allows assessment of the globin genes present in total cellular DNA and is applicable to amniotic-fluid cell DNA. Cellular DNA fragments produced by cleavage using two specific restriction endonucleases are separated on the basis of size by agarose-gel electrophoresis, and the distribution of specific sequences among the DNA fragments determined by molecular hybridization. We observed the total deletion of alpha-globin genes in homozygous alpha-thalassemia (hydrops fetalis with hemoglobin Bart's) and the deletion of particular beta and beta-like sequences in cases homozygous for hereditary persistence of fetal hemoglobin and deltabeta-thalassemia. Analysis of amniotic-fluid cell DNA from a fetus at risk for deltabeta-thalassemia demonstrated the feasibility of these improved methods for antenatal diagnosis. The molecular studies confirmed the diagnosis predicted by analysis of fetal blood and established at birth.