Fetal cells in the maternal circulation: detection of Y-sequence by gene amplification

Detection of a Y-specific sequence in the maternal circulation has clinical importance because it would be useful in determining fetal gender in mothers with severe X-linked disorders. The method described in this paper has the advantage of requiring only small amounts of maternal blood. Numerous attempts have been made to identify XY cells in the blood of mothers bearing male fetuses; however, the results have been controversial. In this study, a member of the DYZ1 family and the XY homologous region of the amelogenin gene were used as targets for polymerase chain reaction detection of the Y chromosome. The subjects in this study were a group of 100 pregnant women at 17-20 weeks' gestation and 30 puerperal women who had given birth 2-5 days previously. All of the former underwent amniocentesis, with venous blood samples drawn before the procedure. Forty-five fetuses were confirmed as male by karyotyping amniocytes, and 30 of these were positive for the Y sequence in the DYZ1 region (sensitivity 66.7%). However, ten of the 55 cases diagnosed as female were also positive, giving a specificity of only 81.8%. Thus, the positive and negative predictive values were each 75%. In the amelogenin gene study, a positive Y signal was not detected in any of the cases examined. This study demonstrates the usefulness of polymerase chain reaction detection of Y-specific sequences in the maternal circulation. However, further investigation is necessary to increase the reliability for clinical application, because the method does produce false-positive results.