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2016 | OriginalPaper | Buchkapitel

7. Pränatale Diagnostik: Molekularbiologische Methoden

verfasst von : Gwendolin Manegold-Brauer, Olav Lapaire, Irene Hösli, Sinuhe Hahn

Verlag: Springer Berlin Heidelberg

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Zusammenfassung

Neben der klassischen Chromosomenuntersuchung im Karyogramm – auch heute noch Goldstandard in der invasiven Pränataldiagnostik – gibt es neuere molekularbiologische Methoden wie z. B. die Polymerasekettenreaktion (PCR) und die Fluoreszenz-in-situ-Hybridisierung (FISH), die die pränatalen diagnostischen Optionen wesentlich erweitert haben und auch in der Präimplantations- und Polkörperchendiagnostik eingesetzt werden, da damit auch monogene Erkrankungen in einzelnen Zellen diagnostiziert werden können.

Durch die Fortschritte bei der Analyse von zellfreier DNA im mütterlichen Blut hat die nichtinvasive pränatale Diagnostik Einzug in den klinischen Alltag gefunden. Mit der massiven parallelen Sequenzierung wird zellfreie DNA von Mutter und Fetus im mütterlichen Blut ohne Risiko für die bestehende Schwangerschaft analysiert. Es ist damit zu rechnen, dass in naher Zukunft neben Chromosomenaberrationen noch viele weitere Erkrankungen mit nichtinvasiven Techniken detektiert werden können.

Vorheriges Kapitel Embryologie und Teratologie

Nächstes Kapitel Fehlbildungsdiagnostik und Ultraschalluntersuchung im 1. Trimenon

Anker P, Stroun M (2000) Circulating DNA in plasma or serum. Medicina (B Aires) 60:699–702

Babochkina T, Mergenthaler S, Lapaire O, Kiefer V, Yura H, Koike K, Holzgreve W, Hahn S (2005) Evaluation of a soybean lectin-based method for enrichment of erythroblasts. J Histochem Cytochem 53:329–330CrossRefPubMed

Benn P, Borrell A, Cuckle H, Dugoff L, Gross S, Johnson JA, Maymon R, Odibo A, Schielen P, Spencer K, Wright D, Yaron Y (2012) Prenatal detection of Down syndrome using massively parallel sequencing (MPS): a rapid response statement from a committee on behalf of the Board of the International Society for Prenatal Diagnosis, 24 October 2011. Prenat Diagn 32(1):1–2CrossRefPubMed

Bianchi DW, Simpson JL, Jackson LG, Elias S, Holzgreve W, Evans MI, Dukes KA, Sullivan LM, Klinger KW, Bischoff FZ, Hahn S, Johnson KL, Lewis D, Wapner RJ, de la Cruz F (2002) Fetal gender and aneuploidy detection using fetal cells in maternal blood: analysis of NIFTY I data. National Institute of Child Health and Development Fetal Cell Isolation Study. Prenat Diagn 22(7):609–615CrossRefPubMed

Bianchi DW, Platt LD, Goldberg JD, Abuhamad AZ, Sehnert AJ, Rava RP (2012) Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstet Gynecol 119:1–13CrossRef

Chan KCA, Ding C, Gerovassili A, Yeung SW, Chiu RWK, Leung TN et al (2006) Hypermethylated RASSF1A in maternal plasma: a universal fetal DNA marker that improves the reliability of noninvasive prenatal diagnosis. Clin Chem 52:2211–2218CrossRefPubMed

Chen XQ, Stroun M, Magnenat JL et al (1996) Microsatellite alterations in plasma DNA of small cell lung cancer patients. Nat Med 2:1033–1035CrossRefPubMed

Chen E, Chiu RWK, Sun H, Akolekar R, Chan K, Leung T et al (2011) Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing. PLoS One 6(7):e21791CrossRefPubMedPubMedCentral

Chiu RW, Murphy MF, Fidler C, Zee BC, Wainscoat JS, Lo YM (2001) Determination of RhD zygosity: comparison of a double amplification refractory mutation system approach and a multiplex real-time quantitative PCR approach. Clin Chem 47:667–672PubMed

Chiu RWK, Akolekar R, Zheng YWL, Leung TY, Sun H, Chan KCA et al (2011) Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study. BMJ 342:c7401CrossRefPubMedPubMedCentral

Clausen FB, Christiansen M, Steffensen R, Jørgensen S, Nielsen C, Jakobsen MA, Madsen RD, Jensen K, Krog GR, Rieneck K, Sprogøe U, Homburg KM, Grunnet N, Dziegiel MH (2012) Report of the first nationally implemented clinical routine screening for fetal RHD in D- pregnant women to ascertain the requirement for antenatal RhD prophylaxis. Transfusion 52(4):752–758CrossRefPubMed

de la Cruz F, Shifrin H, Elias S et al (1995) Prenatal diagnosis by use of fetal cells isolated from maternal blood. Am J Obstet Gynecol 173:1354–1355CrossRefPubMed

Di Naro E, Ghezzi F, Vitucci A et al (2000) Prenatal diagnosis of beta-thalassaemia using fetal erythroblasts enriched from maternal blood by a novel gradient. Mol Hum Reprod 6:571–574CrossRefPubMed

Ehrich M, Deciu C, Zwiefelhofer T, Tynan JA, Cagasan L, Tim R et al (2011) Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting. Am J Obstet Gynecol 204:205.e1–205.e11CrossRef

Eiben B, Trawicki W, Hammans W, Goebel R, Epplen JT (1998) A prospective comparative study on fluorescence in situ hybridization (FISH) of uncultured amniocytes and standard karyotype analysis. Prenat Diagn 18:901–906CrossRefPubMed

Ekelund CK, Jørgensen FS, Petersen OB, Sundberg K, Tabor A, Danish Fetal Medicine Research Group (2008) Impact of a new national screening policy for Down's syndrome in Denmark: population based cohort study. BMJ 337:a2547. doi:10.1136/bmj.a2547CrossRefPubMedPubMedCentral

Evans MI, Henry GP, Miller WA, Bui TH, Snidjers RJ, Wapner RJ, Miny P, Johnson MP, Peakman D, Johnson A, Nicolaides K, Holzgreve W, Ebrahim SA, Babu R, Jackson L (1999) International, collaborative assessment of 146,000 prenatal karyotypes: expected limitations if only chromosome-specific probes and fluorescent in-situ hybridization are used. Hum Reprod 14(5):1213–1216CrossRefPubMed

Fan HC, Blumenfeld YJ, Chitkara U, Hudgins L, Quake SR (2008) Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. Proc Natl Acad Sci U S A 105:16266–167271CrossRefPubMedPubMedCentral

Guex N, Iseli C, Syngelaki A, Deluen C, Pescia G, Nicolaides KH et al (2013) A robust 2nd generation genome-wide test for fetal aneuploidy based on shotgun sequencing cell-free DNA in maternal blood. Prenat Diagn 33(7):707–710CrossRefPubMed

Hahn S, Sant R, Holzgreve W (1998) Fetal cells in maternal blood: current and future perspectives. Mol Hum Reprod 4:515–521CrossRefPubMed

Hahn S, Kiefer V, Brombacher V, Troeger C, Holzgreve W (1999) Fetal cells in maternal blood. An update from Basel. Eur J Obstet Gynecol Reprod Biol 85(1):101–104CrossRefPubMed

Hahn S, Zhong XY, Troeger C, Burgemeister R, Gloning K, Holzgreve W (2000) Current applications of single-cell PCR. Cell Mol Life Sci 57:96–105CrossRefPubMed

Hahn S, Jackson LG et al (2009) Noninvasive prenatal diagnosis of fetal aneuploidies and Mendelian disorders: new innovative strategies. Expert Rev Mol Diagn 9:613–621CrossRefPubMed

Hahn S, Jackson LG, Zimmermann BG (2010) Prenatal diagnosis of fetal aneuploidies: post-genomic developments. Genome Med 2(8):50CrossRefPubMedPubMedCentral

Hahn S, Hösli I, Lapaire O (2012) Non-invasive prenatal diagnostics using next generation sequencing: technical, legal and social challenges. Expert Opin Med Diagn 6(6):517–528CrossRefPubMed

Handyside AH, Pattinson JK, Penketh RJ, Delhanty JD, Winston RM, Tuddenham EG (1989) Biopsy of human preimplantation embryos and sexing by DNA amplification. Lancet 1:347–349CrossRefPubMed

Hardy K, Martin KL, Leese HJ, Winston RM, Handyside AH (1990) Human preimplantation development in vitro is not adversely affected by biopsy at the 8-cell stage. Hum Reprod 5:708–714PubMed

Heid CA, Stevens J, Livak KJ, Williams PM (1996) Real time quantitative PCR. Genome Res 6:986–994CrossRefPubMed

Holzgreve W (1997) Will ultrasound-screening and ultrasound-guided procedures be replaced by non-invasive techniques for the diagnosis of fetal chromosome anomalies? Ultrasound Obstet Gynecol 9:217–219CrossRefPubMed

Holzgreve W (2013) Pränataldiagnostik. Reif für die Praxis? – Die nicht invasive Pränataldiagnostik aus dem Blut Schwangerer. Geburtsh Frauenheilkd 73(8):753–755CrossRef

Holzgreve W, Hahn S (1999) Novel molecular biological approaches for the diagnosis of preeclampsia. Clin Chem 45:451–452PubMed

Holzgreve W, Hahn S (2001) Prenatal diagnosis using fetal cells and free fetal DNA in maternal blood. Clin Perinatol 28:353–365CrossRefPubMed

Holzgreve W, Ghezzi F, Di Naro E, Ganshirt D, Maymon E, Hahn S (1998) Disturbed feto-maternal cell traffic in preeclampsia. Obstet Gynecol 91:669–672PubMed

Holzgreve W, Li JC, Steinborn A, Kulz T et al (2001) Elevation in erythroblast count in maternal blood before the onset of preeclampsia. Am J Obstet Gynecol 184:165–168CrossRefPubMed

Hulett HR, Bonner WA, Barrett J, Herzenberg LA (1969) Cell sorting: automated separation of mammalian cells as a function of intracellular fluorescence. Science 166:747–749CrossRefPubMed

Kagan KO, Hoopmann M, Kozlowski P (2012) Assessment of foetal DNA in maternal blood – A useful tool in the hands of prenatal specialists. Geburtsh Frauenheilkd 72:998–1003CrossRef

Kim YA, Makar RS (2012) Detection of fetomaternal hemorrhage. Am J Hematol 87(4):417–423CrossRefPubMed

Kitagawa M, Sugiura K, Omi H, Akiyama Y, Kanayama K, Shinya M, Tanaka T, Yura H, Sago H (2002) New technique using galactose-specific lectin for isolation of fetal cells from maternal blood. Prenat Diagn 22(1):17–21CrossRefPubMed

Klinger K, Landes G, Shook D et al (1992) Rapid detection of chromosome aneuploidies in uncultured amniocytes by using fluorescence in situ hybridization (FISH). Am J Hum Genet 51:55–65PubMedPubMedCentral

Lapaire O, Holzgreve W, Oosterwijk JC, Brinkhaus R, Bianchi DW (2007a) Georg Schmorl on trophoblasts in the maternal circulation. Placenta 28(1):1–5CrossRefPubMed

Lapaire O, Lu XY, Johnson KL, Jarrah Z, Stroh H, Cowan JM, Tantravahi U, Bianchi DW (2007b) Array-CGH analysis of cell-free fetal DNA in 10 mL of amniotic fluid supernatant. Prenat Diagn 27(7):616–621CrossRefPubMed

Lapaire O, Hösli I, Tercanli S, Holzgreve W (2008) Rhesusfaktor-Bestimmung des Fetus aus dem Blut der Schwangeren: nichtinvasive genetische Diagnostik mit Konsequenz für die Praxis? Schweiz Med Forum 8:17–18

Leung TN, Zhang J, Lau TK, Chan LY, Lo YM (2001) Increased maternal plasma fetal DNA concentrations in women who eventually develop preeclampsia. Clin Chem 47:137–139PubMed

Li Y, Zimmermann B, Zhong XY, Gupta AK, Holzgreve W, Hahn S (2003) Determination of RHD zygosity using real-time quantitative PCR. Swiss Med Wkly 133:4442–4445

Li Y, Zimmermann B, Rusterholz C, Kang A, Holzgreve W, Hahn S (2004) Size separation of circulatory DNA in maternal plasma permits ready detection of fetal DNA polymorphisms. Clin Chem 50(6):1002–1011CrossRefPubMed

Li Y, Di Naro E, Vitucci A, Zimmermann B, Holzgreve W, Hahn S (2005a) Detection of paternally inherited fetal point mutations for beta-thalassemia using size-fractionated cell-free DNA in maternal plasma. JAMA 293(7):843–849CrossRefPubMed

Li Y, Holzgreve W, Page-Christiaens GC, Gille JJ, Hahn S (2005b) Improved prenatal diagnosis of a fetal point mutation for achondroplasia by the use of size-fractionated circulatory DNA in maternal plasma – case report. Prenat Diagn 24(11):896–898CrossRef

Lo YM (1999) Fetal RhD genotyping from maternal plasma. Ann Med 31:308–312CrossRefPubMed

Lo YM, Corbetta N, Chamberlain PF et al (1997) Presence of fetal DNA in maternal plasma and serum. Lancet 350:485–487CrossRefPubMed

Lo YM, Tein MS, Lau TK et al (1998) Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet 62:768–775CrossRefPubMedPubMedCentral

Lo YM, Lau TK, Zhang J et al (1999) Increased fetal DNA concentrations in the plasma of pregnant women carrying fetuses with trisomy 21. Clin Chem 45:1747–1751PubMed

Manegold-Brauer G, Kang Bellin A, Hahn S, De Geyter C, Buechel J, Hoesli I, Lapaire O (2014) A new era in prenatal care: non-invasive prenatal testing in Switzerland. Swiss Med Wkly 144:w13915. doi:10.4414/smw.2014.13915PubMed

Manegold-Brauer G, Berg C, Flöck A, Rüland A, Gembruch U, Geipel A. (2015) Uptake of non-invasive prenatal testing (NIPT) and impact on ivasive procedures in a tertiary referral center. Arch Gynecol Obstet. Feb 26, Epub vor der Druckversion

Mann K, Fox SP, Abbs SJ et al (2001) Development and implementation of a new rapid aneuploidy diagnostic service within the UK National Health Service and implications for the future of prenatal diagnosis. Lancet 358:1057–1061CrossRefPubMed

Mergenthaler S, Babochkina T, Kiefer V, Lapaire O, Holzgreve W, Hahn S (2005) FISH analysis of all fetal nucleated cells in maternal blood: improved specificity by the use of two Y-chromosome probes. J Histochem Cytochem 53(2):319–322CrossRefPubMed

Mullis K, Faloona F, Scharf S, Saiki R, Horn G, Erlich H (1986) Specific enzymatic amplification of DNA in vitro: the polymerase chain reaction. Cold Spring Harb Symp Quant Biol 51:263–273CrossRefPubMed

Newton CR, Graham A, Heptinstall LE et al (1989) Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucleic Acids Res 17:2503–2516CrossRefPubMedPubMedCentral

Nicolini U et al (2004) The introduction of QF-PCR in prenatal diagnosis of fetal aneuploidies: time for reconsideration. Hum Reprod Update 10(6):541–548CrossRefPubMed

Norton ME, Brar H, Weiss J, Karimi A, Laurent LC, Caughey AB et al (2012) Non-Invasive Chromosomal Evaluation (NICE) Study: results of a multicenter prospective cohort study for detection of fetal trisomy 21 and trisomy 18. Am J Obstet Gynecol 207:1–8CrossRef

Palomaki GE, Kloza EM, Lambert-Messerlian GM, Haddow JE, Neveux LM, Ehrich M, van den Boom D, Bombard AT, Deciu C, Grody WW, Nelson SF, Canick JA (2011) DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study. Genet Med 13(11):913–920. doi:10.1097/GIM.0b013e3182368a0eCrossRefPubMed

Radbruch A, Mechtold B, Thiel A, Miltenyi S, Pfluger E (1994) High-gradient magnetic cell sorting. Methods Cell Biol 42:387–403CrossRefPubMed

Ried T, Schrock E, Ning Y, Wienberg J (1998) Chromosome painting: a useful art. Hum Mol Genet 7:1619–1626CrossRefPubMed

Sanger F, Donelson JE, Coulson AR, Kossel H, Fischer D (1973) Use of DNA polymerase I primed by a synthetic oligonucleotide to determine a nucleotide sequence in phage fl DNA. Proc Natl Acad Sci U S A 70:1209–1213CrossRefPubMedPubMedCentral

Schröck E, du Manoir S, Veldman TJ et al (1996) Multicolor spectral karyotyping of human chromosomes. Science 273:494–497CrossRefPubMed

Sparks AB, Struble CA, Wang ET, Song K, Oliphant A (2012) Non-invasive prenatal detection and selective analysis of cell-free DNA obtained from maternal blood: evaluation for trisomy 21 and trisomy 18. Am J Obstet Gynecol 206:322.e1–322.e5CrossRef

Troeger C, Zhong XY, Burgemeister R et al (1999) Approximately half of the erythroblasts in maternal blood are of fetal origin. Mol Hum Reprod 5:1162–1165CrossRefPubMed

Valenti C, Schutta EJ, Kehaty T (1968) Prenatal diagnosis of Down’s syndrome. Lancet ii:220CrossRef

Verlinsky Y, Cohen J, Munne S, Gianaroli L, Simpson JL, Ferraretti AP, Kuliev A (2004) Over a decade of experience with preimplantation genetic diagnosis: a multicentre report. Fertil Steril 82(2):292–294CrossRefPubMed

Verma L, Macdonald F, Leedham P, McConachie M, Dhanjal S, Hulten M (1998) Rapid and simple prenatal DNA diagnosis of Down’s syndrome. Lancet 352:9–12CrossRefPubMed

Wells D, Delhanty JD (2001) Preimplantation genetic diagnosis: applications for molecular medicine. Trends Mol Med 7:23–30CrossRefPubMed

Zhong XY, Burk MR, Troeger C, Jackson LR, Holzgreve W, Hahn S (2000) Fetal DNA in maternal plasma is elevated in pregnancies with aneuploid fetuses. Prenat Diagn 20:795–798CrossRefPubMed

Zhong XY, Hahn S, Holzgreve W (2001a) Prenatal identification of fetal genetic traits. Lancet 357:310–311CrossRefPubMed

Zhong XY, Holzgreve W, Hahn S (2001b) Circulatory fetal and maternal DNA in pregnancies at risk and those affected by preeclampsia. Ann N Y Acad Sci 945:138–140CrossRefPubMed

Titel: Pränatale Diagnostik: Molekularbiologische Methoden
verfasst von: Gwendolin Manegold-Brauer
Olav Lapaire
Irene Hösli
Sinuhe Hahn
Verlag: Springer Berlin Heidelberg
Buch: Die Geburtshilfe
Print ISBN: 978-3-662-45063-5

Electronic ISBN: 978-3-662-45064-2

Copyright-Jahr: 2016
DOI: https://doi.org/10.1007/978-3-662-45064-2_7

Springerpflege

Zusammenfassung

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