Advances in the prenatal diagnosis of hematologic diseases
BP Alter
Prenatal diagnosis of hematologic diseases can now be performed with fetal
blood, fetal amniotic fluid cell DNA, and fetal chorionic villi DNA. Some
hemoglobinopathies can be detected by all three methods, and the choice
will depend on the available obstetric and laboratory techniques, as well
as the time of presentation of the pregnancy. Hopefully, further
development of molecular probes and techniques will soon expand these
options to all of the globin disorders. Detection of coagulation disorders
in utero currently requires samples of pure fetal blood. Gene cloning is
accomplished for some (factor IX and antithrombin III) and is underway for
others (factor VIII), and further investigation is necessary to determine
whether deficiencies in these gene products are due to gene deletion or to
mutant genes linked to polymorphic restriction enzyme sites of diagnostic
use. Thus, molecular biology may be applied to prenatal diagnosis of the
clotting problems, but this has not yet been accomplished. Disorders
affecting the number and/or function of erythrocytes, leukocytes, and
platelets can be diagnosed by analysis of fetal blood. Blood samples will
continue to be required until more is known about the molecular biology of
hematopoiesis. Syndromes that can be diagnosed by chromosome studies should
be revealed in cultures of amniotic fluid cells, fetal blood lymphocytes,
and chorionic villi cells. Cultured cells can be examined for karyotypes,
Y-chromatin, spontaneous or induced chromosome breakage, DNA repair, SCEs,
and translocations. The techniques for culturing amniotic cells and fetal
blood white cells are established, and those for growing cells from
chorionic villi are improving rapidly. Direct preparations of cells from
villi only may suffice for some of the above analyses. The study of
hematologic disease in utero has thus come full circle, from the use of
amniotic cells to determine the sex in X-linked disorders, to fetal blood
sampling for the analysis of gene products, then back to amniocentesis for
DNA, and now earlier in gestation to chorionic villi. All of this has
occurred in less than ten years, and it is anticipated that developments in
the next ten years will be equally dramatic. The future should bring all
prenatal testing into the first trimester, use molecular probes, and
provide for both early diagnosis and early treatment of genetic hematologic
disease.
Volume 64,
Issue 2,
pp. 329-340,
08/01/1984
Copyright © 1984 by The American Society of Hematology
