Prenatal diagnosis of Chinese homozygous alpha-thalassaemia 1 and haemoglobin H disease by analysis of alpha- and phi zeta-globin genes in chorionic villi and amniocytes.

Eighty-eight high-risk pregnancies, 81 for homozygous alpha-thalassaemia 1 and 7 for haemoglobin (Hb) H disease, were collected in this study. Chorionic villus sampling (CVS) was done in 63 cases and amniocentesis in 25 cases to obtain fetal cells. Southern blotting and DNA hybridization with alpha- and phi zeta-globin gene probes were used to determine the alpha-globin gene status. In two non-informative families with non-deletional mutations, DNA analysis failed to rule out the affected condition, and fetal blood sampling (FBS) and Hb electrophoresis were used for the final diagnosis. In the 81 fetuses at risk for homozygous alpha-thalassaemia 1, 17 (13 by CVS and 4 by amniocentesis) were affected, 30 were alpha-thalassaemia 1 heterozygotes, 19 were normal, and the remaining 15 were either normal or heterozygous. In the seven fetuses at risk for Hb H disease, one was normal, three were alpha-thalassaemia 1 heterozygotes, two were alpha-thalassaemia 2 heterozygotes, and one was affected with Hb H disease and developed hydrops fetalis. DNA analysis on fetal cells enabled us to diagnose prenatally severe alpha-thalassaemias, to prevent the birth of infants with Hb H disease, and to minimize maternal obstetrical complications from harbouring a fetus with Hb Bart's hydrops fetalis.