Prenatal diagnosis of fanconi anemia: Functional and molecular testing

A. Bechtold, R. Kalb, K. Neveling, R. Friedl, B. Gottwald, S. Herterich, M. Schmugge Liner, C. Heilmann, H. Hanenberg, D. Schindler

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations


There are two main approaches to the prenatal confirmation or exclusion of Fanconi anemia: functional testing and molecular testing. Functional testing involves the determination of crosslink sensitivity either by chromosome breakage analysis or cell cycle testing. Indications for functional testing include ultrasonographic findings of radial ray defects in the absence of a family history of FA, but also testing of at risk pregnancies in families with a prior affected child where for various reasons there is no information on complementation group and disease causing mutations. Since laboratories offering functional prenatal testing mostly use analysis of chromosome breakage, we here summarize our experience with flowcytometric testing of MMC-sensitivity in second trimester amniotic fluid cell cultures. We show that among a series of 20 pregnancies at risk three amniotic fluid cell cultures were highly sensitive to MMC as evidenced by their strong G2-phase elevations after exposure to 10 ng/ml of the drug. There were no false positives and no false negatives among our series suggesting single parameter flowcytometry as a speedy and reliable alternative to conventional chromosome breakage studies for the prenatal diagnosis of FA in situations where only functional testing can be performed. Molecular testing of course is the method of choice but requires prior knowledge of complementation group and mutations. Indirect genetic testing is possible if at least the complementation group is known and DNAs from both parents and an affected child are available. With the availability of retroviral vectors for rapid subtyping, and owing to advances in high-throughput mutation analysis including MLPA, direct molecular genetic testing is likely to replace functional testing for most but not all risk pregnancies in the near future. We illustrate the practice of direct prenatal genetic testing with examples from families belonging to complementation groups FA-A, FA-C, FA-G and FA-D2. Last but not least we comment on the implications of preimplantation genetic testing (PGD) as a high-tech but problematic procedure to preselect potential HLA-matched sibling donors.

Original languageEnglish (US)
Title of host publicationFanconi Anemia
Subtitle of host publicationA Paradigmatic Disease for the Understanding of Cancer and Aging
EditorsHolger Hoehn, Detlev Schindler
Number of pages18
StatePublished - Dec 1 2007

Publication series

NameMonographs in Human Genetics
ISSN (Print)0077-0876
ISSN (Electronic)1662-3835

ASJC Scopus subject areas

  • Genetics(clinical)

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    Bechtold, A., Kalb, R., Neveling, K., Friedl, R., Gottwald, B., Herterich, S., Liner, M. S., Heilmann, C., Hanenberg, H., & Schindler, D. (2007). Prenatal diagnosis of fanconi anemia: Functional and molecular testing. In H. Hoehn, & D. Schindler (Eds.), Fanconi Anemia: A Paradigmatic Disease for the Understanding of Cancer and Aging (pp. 131-148). (Monographs in Human Genetics; Vol. 15).