Application of molecular genetics to prenatal diagnosis and carrier
detection in the hemophilias: some limitations
JB Graham, PP Green, RA McGraw and LM Davis
Prenatal diagnosis and carrier detection in the hemophilias have received
much attention in recent years. The error rate in prenatal diagnosis by
fetoscopy is less than 1%; fetoscopy is not possible, however, until the
second trimester of pregnancy. Carrier detection based on bioassays of
plasma has an irreducible error rate (approximately 5%?), because of the
"lyonization" phenomenon in heterozygous women, and the final results are
always probabilistic. New DNA methods promise to alleviate these
difficulties. Prenatal diagnosis can be accomplished in the first
trimester. "Lyonization" is bypassed in carrier detection, and the results
may sometimes be essentially nonprobabilistic. But the DNA methods have
certain limitations of their own which are not widely appreciated. Aside
from cost and the necessity to adopt a new technology, there are inherent
genetic problems: mothers must be heterozygous for both a disease gene and
a marker gene, final results are probabilistic if the marker gene lies
outside the disease gene, and multiple marker genes are often in linkage
disequilibrium. We have concluded that a clinical unit planning to use the
DNA methods must also maintain the conventional methods at a high level of
performance.
Volume 66,
Issue 4,
pp. 759-764,
10/01/1985
Copyright © 1985 by The American Society of Hematology
