731 PRENATAL DIAGNOSIS OF β-THALASSEMIA BY AMNIO-CENTESIS

Abstract

We have conducted prenatal diagnosis for β-thalassemia (thal) by analysis of fetal DNA of amniotic fluid cells from 9 women at risk for affected children (4 Italian, 2 Greek, 2 Asiatic Indian, 1 Chinese). DNA of parents and their previous affected child was examined at 4 polymorphic restriction endonuclease sites near the thal mutation. Studies of an affected child allow us to determine which sites are “marking” the thal genes. One can then use linkage analysis to diagnose the thal status of the fetus. In 4 of the 9 fetuses studied, normal, thal trait, and affected genotypes could be differentiated. Diagnoses were: 1 normal, 1 affected, and 1 thal trait fetus; the latter 2 were confirmed by fetoscopy. Tests on the fourth fetus are pending. In the remaining 5 fetuses, thal major could be excluded in 3, but not in 2, both of which underwent fetoscopy. Screening of 20 additional couples at risk has shown that in 75% of their future pregnancies either exact fetal thal status can be determined or thal major can be ruled out. These results suggest that amniocentesis, with its low fetal risk and wide availability, can be the primary approach to prenatal diagnosis of β-thalassemia.