title: 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.
mesh_terms: D000328:Adult; D000653:Amniotic Fluid / Q000032:analysis / Q000166:cytology; D001483:Base Sequence; D004247:DNA; D004720:Endonucleases; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis; D005796:Genes; D005914:Globins / Q000032:analysis / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012306:Risk; D013789:Thalassemia / Q000175:diagnosis* / Q000235:genetics
chemical_list: D005914:Globins; D004247:DNA; D005319:Fetal Hemoglobin; D004720:Endonucleases