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

Abstract

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.

• Authors: S H Orkin, B P Alter, C Altay, M J Mahoney, H Lazarus, J C Hobbins, D G Nathan
• Journal: The New England journal of medicine (N Engl J Med) Vol. 299 Issue 4 Pg. 166-72 (Jul 27 1978) ISSN: 0028-4793 [Print] United States
• PMID: 661890 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Globins
• DNA
• Fetal Hemoglobin
• Endonucleases

Topics

• Adult
• Amniotic Fluid (analysis, cytology)
• Base Sequence
• DNA
• Endonucleases
• Female
• Fetal Hemoglobin (analysis)
• Genes
• Globins (analysis, genetics)
• Homozygote
• Humans
• Infant, Newborn
• Mutation
• Pregnancy
• Prenatal Diagnosis
• Risk
• Thalassemia (diagnosis, genetics)