Prenatal diagnosis of α- and β-thalassemias: Experience in Hong Kong

Abstract

The incidence of α-thalassemia trait (α-thal-1 and α-thal-2) among Southern Chinese in Hong Kong is about 3%. From June 1983 to September 1987, prenatal diagnosis for homozygous α-thal-1 was performed in 88 pregnancies at risk, using direct DNA analysis of amniotic fluid cells or chorionic villi. Twenty-one homozygous α-thal-1 fetuses were aborted and confirmed as Hb Bart's hydrops fetalis, and two were 'Hb H' hydrops fetalis. Of 47 pregnancies delivered, 26 were α-thal-1 heterozygotes, 10 normal, eight α-thal-l/normal. Twenty-one pregnancies, diagnosed as α-thal-l/normal, await delivery. Based on a 6% incidence of β-thalassemia minor among pregnant women in Hong Kong, the number of pregnancies at risk for β-thalassemia major should be 288 per annum. However, since February 1984, only 25 diagnoses were performed. Comprehensive screening and education programs need to be implemented. The majority of β-thalassemia defects in Southern Chinese are point mutations, single nucleotide insertions or minor deletions, not detectable by standard gene mapping techniques. With linkage analysis of the defective gene to polymorphic restriction sites, a definitive diagnosis can be obtained in 50% of the families, while in the remaining there is a 50% exclusion rate. We routinely use the Hind III-3'β, Bam HI-3'β, Ava II-β, and Hinc II-ψβ sites for linkage analysis. For first pregnancies, the marked linkage disequilibrium of the Bam HI polymorphism can be applied in 29% of the cases. In nonconclusive cases, fetal blood β/γ globin chain synthetic ratio was used. Results to date include: seven β-thalassemia major (aborted), 10 β-thalassemia minor, two normals, and six β-thalassemia minor/normal pending delivery. Determination of four diferent mutations, detectable by oligonucleotide probes, would allow us in the future to diagnose 87% of the cases at risk for β-thalassemia major.