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 Citation (Scopus)

Abstract

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 publicationMonographs in Human Genetics
Pages131-148
Number of pages18
Volume15
DOIs
StatePublished - 2007
Externally publishedYes

Publication series

NameMonographs in Human Genetics
Volume15
ISSN (Print)00770876
ISSN (Electronic)16623835

Fingerprint

Fanconi Anemia
Genetic Testing
Prenatal Diagnosis
Chromosome Breakage
Amniotic Fluid
Pregnancy
Mutation
Cell Culture Techniques
Prostaglandins D
G2 Phase
Second Pregnancy Trimester
Siblings
Molecular Biology
Cell Cycle
Parents
Tissue Donors
DNA
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Bechtold, A., Kalb, R., Neveling, K., Friedl, R., Gottwald, B., Herterich, S., ... Schindler, D. (2007). Prenatal diagnosis of fanconi anemia: Functional and molecular testing. In Monographs in Human Genetics (Vol. 15, pp. 131-148). (Monographs in Human Genetics; Vol. 15). https://doi.org/10.1159/000102553

Prenatal diagnosis of fanconi anemia : Functional and molecular testing. / Bechtold, A.; Kalb, R.; Neveling, K.; Friedl, R.; Gottwald, B.; Herterich, S.; Liner, M. Schmugge; Heilmann, C.; Hanenberg, H.; Schindler, D.

Monographs in Human Genetics. Vol. 15 2007. p. 131-148 (Monographs in Human Genetics; Vol. 15).

Research output: Chapter in Book/Report/Conference proceedingChapter

Bechtold, A, Kalb, R, Neveling, K, Friedl, R, Gottwald, B, Herterich, S, Liner, MS, Heilmann, C, Hanenberg, H & Schindler, D 2007, Prenatal diagnosis of fanconi anemia: Functional and molecular testing. in Monographs in Human Genetics. vol. 15, Monographs in Human Genetics, vol. 15, pp. 131-148. https://doi.org/10.1159/000102553
Bechtold A, Kalb R, Neveling K, Friedl R, Gottwald B, Herterich S et al. Prenatal diagnosis of fanconi anemia: Functional and molecular testing. In Monographs in Human Genetics. Vol. 15. 2007. p. 131-148. (Monographs in Human Genetics). https://doi.org/10.1159/000102553
Bechtold, A. ; Kalb, R. ; Neveling, K. ; Friedl, R. ; Gottwald, B. ; Herterich, S. ; Liner, M. Schmugge ; Heilmann, C. ; Hanenberg, H. ; Schindler, D. / Prenatal diagnosis of fanconi anemia : Functional and molecular testing. Monographs in Human Genetics. Vol. 15 2007. pp. 131-148 (Monographs in Human Genetics).
@inbook{eb989f031002424fae49c2d46395011d,
title = "Prenatal diagnosis of fanconi anemia: Functional and molecular testing",
abstract = "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.",
author = "A. Bechtold and R. Kalb and K. Neveling and R. Friedl and B. Gottwald and S. Herterich and Liner, {M. Schmugge} and C. Heilmann and H. Hanenberg and D. Schindler",
year = "2007",
doi = "10.1159/000102553",
language = "English (US)",
isbn = "9783805582773",
volume = "15",
series = "Monographs in Human Genetics",
pages = "131--148",
booktitle = "Monographs in Human Genetics",

}

TY - CHAP

T1 - Prenatal diagnosis of fanconi anemia

T2 - Functional and molecular testing

AU - Bechtold, A.

AU - Kalb, R.

AU - Neveling, K.

AU - Friedl, R.

AU - Gottwald, B.

AU - Herterich, S.

AU - Liner, M. Schmugge

AU - Heilmann, C.

AU - Hanenberg, H.

AU - Schindler, D.

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84870162678&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84870162678&partnerID=8YFLogxK

U2 - 10.1159/000102553

DO - 10.1159/000102553

M3 - Chapter

SN - 9783805582773

VL - 15

T3 - Monographs in Human Genetics

SP - 131

EP - 148

BT - Monographs in Human Genetics

ER -