Prenatal exclusion/confirmation of Fanconi anemia via flow cytometry: a pilot study.
OBJECTIVE
To explore the potential of flow cytometry in the prenatal exclusion or confirmation of Fanconi anemia (FA).


METHODS
Indications for prenatal diagnosis were (1) FA-negative family history, but suspicious ultrasound findings such as radial ray aplasia, (2) FA-positive family history, but without knowledge of the affected gene and/or mutation. Amniotic fluid (AF) cell cultures and umbilical cord (UC) blood cultures were assayed for typical cell cycle changes (G2-phase accumulations) without and with mitomycin C (MMC) treatments using single- and dual-parameter (BrdU-Hoechst) flow cytometry.


RESULTS
Single-parameter flow cytometry correctly identified 2 positive and 9 negative cases on the basis of MMC sensitivity of cultivated AF cells. Likewise, 8 negative and 2 positive cases were correctly predicted using bivariate flow cytometry of 72-hour UC blood cultures. In contrast, bivariate flow cytometry applied to AF cells grown in the presence of bromodeoxyuridine (BrdU) yielded false-positive and false-negative results.


CONCLUSIONS
Single-parameter flow cytometry of AF cell cultures and bivariate flow cytometry of UC cell cultures have the potential to correctly predict the affected status in cases at risk for FA, whereas bivariate flow cytometry proved unreliable when applied to BrdU-substituted AF cell cultures. Cases with a low a priori risk (e.g. sonographic finding of radial ray abnormalities and negative family history) would benefit most from flow cytometry as a rapid and economical prenatal screening procedure.
Bechtold
Astrid
A
Department of Human Genetics, University of Wurzburg School of Medicine, Wurzburg, Germany.
Friedl
Richard
R
Kalb
Reinhard
R
Gottwald
Benni
B
Neveling
Kornelia
K
Gavvovidis
Ioannis
I
Herterich
Sabine
S
Schindler
Detlev
D
Hoehn
Holger
H
D000649:Amniocentesis; D000653:Amniotic Fluid / Q000166:cytology*; D002478:Cells, Cultured; D005199:Fanconi Anemia / Q000175:diagnosis* / Q000196:embryology; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D010865:Pilot Projects; D011247:Pregnancy; D011296:Prenatal Diagnosis