Prenatal diagnosis of hemoglobin H disease.

Hemoglobin H disease was diagnosed prior to the twenty-second week of gestation in a pregnancy at risk for homozygous alpha-thalassemia using the technique of DNA-DNA hybridization. Fetal DNA was obtained from amniotic fluid fibroblasts obtained during the thirteenth week of gestation and grown in culture. The fetal fibroblast DNA was hybridized to radioactive alpha-globin cDNA. The number of alpha-globin genes present in the fetus was determined by comparing results of hybridization studies on the fetal DNA to similar studies on subjects with well-defined alpha-thalassemia syndromes and with normal subjects. The diagnosis of hemoglobin H disease was confirmed at birth by studies of the cord blood. This study confirms the ability of DNA-DNA hybridization techniques to distinguish the three-gene defect of hemoglobin H disease from the lethal four-gene defect of homozygous alpha-thalassemia.