Detecting Fetal Genetic Mutations in Maternal Plasma

A novel process utilizing mass spectrometry has been developed to determine beta-thalassemia mutations in circulating fetal nucleic acids in maternal plasma to aid prenatal diagnosis in at-risk pregnancies.

An international consortium developed the process, led by the Chinese University of Hong Kong (CUHK), Boston University (BU, MA, USA) and Sequenom, Inc. (San Diego, CA, USA). The process was described in the July 9, 2004, online Early Edition of the Proceedings of the [U.S.] National Academy of Sciences.

The investigators, led by CUHK's Rossa W.K. Chiu, M.D., Ph.D., and BU's Chunming Ding, Ph.D., used the MassArray technology of Sequenom to detect the inheritance of the four most common Southeast Asian beta-thalassemia mutations in at-risk pregnancies between seven and 21 weeks of gestation, and to analyze fetal haplotypes based on a genetic variation linked to the beta-blobin locus HBB.

"Utilizing the superior sensitivity and specificity of the MassArray system, we have been able to isolate certain fetal point mutations and haplotypes in a noninvasive procedure with no risk to the fetus,” explained Charles R.Cantor, Ph.D., chief scientific officer of Sequenom.

This development is very exciting and has addressed a long-awaited need in noninvasive prenatal diagnosis, according to Y.M. Dennis Lo, D.M., of CUHK, who discovered the presence of fetal DNA in maternal plasma in 1997 and directs the international consortium. "In addition to beta-thalassemia, the platform can be readily applied to many other diseases of importance in prenatal diagnosis, e.g., cystic fibrosis. We also anticipate important applications in oncology, where tumor-associated genetic mutations can be detected in the patient's blood plasma.”

The method is based on Sequenom's MassArray technology and a new protocol called single allele base extension reaction (SABER), where primer extension is restricted to the fetal specific allele. The approach eliminates the significant risk of fetal loss associated with current invasive prenatal testing techniques, such as amniocentesis and chorionic villus sampling. Sequenom believes the MassArray platform-supported approach is potentially applicable to other areas requiring genetic trace analysis, such as early cancer detection.



Related Links:
Chinese U. of Hong Kong
Boston U.
Sequenom