Antenatal diagnosis of sickle cell anaemia by direct analysis of the sickle mutation

Abstract

Sickle cell anemia was detected antenatally by restriction analysis with the enzyme Dde I, which cleaves normal human DNA at the position corresponding to aminoacid number 6 of the beta-globin chain. This site is abolished by the mutation in sickle cell disease, and hence different-sized fragments are generated on digestion of normal and sickle genes with this enzyme. In a pregnancy at risk for sickle cell anaemia, digestion of DNA from cultured amniotic fluid cells revealed a pattern indicating the haemoglobin AA genotype. The diagnosis was later confirmed by fetal blood analysis. The test proved applicable to the sickle gene from Africa, Asia, The Middle East, and two Mediterranean countries.