Antenatal diagnosis of sickle cell disease: amniotic fluid cell DNA analysis.

Using recombinant DNA methods and amniocentesis, the antenatal diagnosis of sickle cell disorders can be accomplished. This article presents the authors' experiences with 21 pregnancies at risk using HpaI and Hind III restriction enzyme digestions of adult leukocytic and fetal amniotic fluid cell DNA. The authors were able to establish direct beta A- and beta S-globin gene linkages to the restricted fragments in 9 families. In 8 families no direct linkages could be determined and estimates of exclusion of fetal beta S homozygosity were used. These estimates were made on the basis of the frequencies of association of the HpaI fragments with the beta S and beta A genes in the Afro-American population. In 4 families, no estimates or linkages could be established, and the patients were counseled in reference to fetoscopy. The data also indicated the frequencies of association of the HpaI fragments with the beta A and beta S gene in the New Jersey-New York population. These studies did not seem to indicate any exclusive preferential segregation of the HpaI and Hind III polymorphisms.