Abstract
Fluorescence in situ hybridization provides a rapid and accurate technique for detecting chromosomal aneuploidy. It is an excellent method for identifying mosaicism in placental tissues following prenatal diagnosis. Mosaicism, in the form of confined placental mosaicism, occurs im approximately 1%–2% of viable pregnancies studied by chorionic villus sampling at 9–11 weeks of gestation. It has been detected in pregnancies with both diploid and trisomic fetuses and appears to have an important effect on the intrauterine fetal survival. Using both standard cytogenetic analysis and fluorescence in situ hybridization, we have studied 12 placentas from pregnancies with trisomy 18 for the presence of chromosomal mosaicism. These included 2 that were spontaneously aborted, 5 that were terminated after prenatal diagnosis, and 4 that were delivered as either stillborn or liveborn. Significant levels of mosaicism, confined exclusively to cytotrophoblast, were detected in 7 pregnancies. This study demonstrates the usefulness of interphase cytogenetic analysis of uncultured tissues as an alternative method for the detection of mosaicism.
Similar content being viewed by others
References
Bajalica S, Bui T-H, Koch J, et al (1992) Prenatal investigation of a 45,X/46,X(r?) karyotype in amniocytes using fluorescence in situ hybridization with an X-centromeric probe. Prenat Diagn 12:61–64
Binkert F, Savoldelli G, Hungentobler W, et al (1989) Chorionic villus sampling (placenta biopsy) in the second and third trimester: cytogenetic results in 111 cases. In: Antsaklis A, Metaxotou C (eds) Chorionic villus sampling and early prenatal diagnosis. BETA Medical Arts, Athens, pp 138–141
Breed ASPM, Mantingh A, Vosters R, Beekhus JR, Van Lith JMM, Anders GJPA (1991) Follow-up and pregnancy outcome after a diagnosis of mosaicism in CVS. Prenat Diagn 11:577–580
Cartier L, Vekemans M, Hamilton E (1988) Occurrence and interpretation of discordance in cytogenetic analysis of chorionic villi. Am J Hum Genet 43 [Suppl]:A255
Christensen B, Bryndorf T, Philip J, Lundsteen C, Hansen W (1991) Rapid prenatal diagnosis of trisomy 18 and triploidy in interphase nuclei of uncultured amniocytes by nonradioactive in situ hybridization. Prenat Diagn 12:241–250
Cox DM, Niewczas-Late V, Riffel MI, Hamerton JL (1974) Chromosome mosaicism in diagnostic amniotic fluid cell cultures. Pediatr Res 8:679–683
Hahn GJ, Meeker WQ (1991) Statistical intervals: a guide for practitioners. Wiley, New York
Heim S, Kristoffersson U, Mandahl N, Mineur A, Mitelman F, Edvall H, Gustavii B (1985) Chromosome analysis in 100 cases of first trimester trophoblast sampling. Clin Genet 27:451–457
Herrington CS, McGee JO'D (1990) Interphase cytogenetics. Neurochem Res 15:467–474
Jacobs P, Hassold T (1987) Chromosome abnormalities: origin and etiology in abortions and livebirths. In: Vogel F, Sperling K (eds) Human genetics. Springer, Berlin Heidelberg New York
Johnson A, Wapner RJ, Davis GH, Jackson LG (1990) Mosaicism in chorionic villus sampling: an association with poor perinatal outcome. Obstet Gynecol 75:573–577
Kalousek DK, Barrett U, McGillivray BC (1989) Placental mosaicism and intrauterine survival of trisomics 13 and 18. Am J Hum Genet 44:338–343
Kalousek DK, Howard-Peebles PN, Olson SB, Barrett IJ, Dorfmann A, Black SH, Schulman JD, Wilson RD (1991) Confirmation of CVS mosaicism in term placentae and high frequency of intrauterine growth retardation association with confined placental mosaicism. Prenat Diagn 11:743–750
Kalousek DK, Langlois S, Barrett IJ, Yam I, Wilson DR, Howard-Peebles PN, Johnson MP, Giorgiutti E (1993) Uniparental disomy for chromosome 16 in humans. Hum Genet 52:8–16
Klever M, Grond-Ginsbach CJ, Hager H-D, Schroeder-Kurth TM (1992) Chorionic villus metaphase chromosomes and interphase nuclei analyzed by chromosomal in situ hybridization. Prenat Diagn 12:53–59
Klinger K, Landes G, Shook D, Harvey R, Lopez L, Locke P, Lerner T, Osathanondh R, Leverone B, Houseal T, Pavelka K, Dackowski W (1992) Rapid detection of chromosome aneuploidy in uncultured amniocytes by using fluorescence in situ hybridization (FISH). Am J Hum Genet 51:55–65
Kuo W-L, Tenjin H, Segraves R, Pinkel D, Golbus MS, Gray J (1992) Detection of aneuploidy involving chromosomes 13, 18,or 21, by fluorescence in situ hybridization (FISH) to interphase and metaphase amniocytes. Am J Hum Genet 49:112–119
Ledbetter DH, Zachary JM, Simpson JL, Golbus MS, Pergament E, Jackson L, Mahoney MJ, Desnick RJ, Schulman J, Copeland KL, Verlinsky Y, Yang-Feng T, Schonberg SA, Babu A, Tharapel A, Dorfmann A, Lubs HA, Rhoads GG, Fowler E, De la Cruz F (1992) Cytogenetic results from the US collaborative study on CVS. Prenat Diagn 12:317–345
Martin AO, Elias S, Rosinsky B, Bombard AT, Simpson JL (1986) False negative finding on chorionic villus sampling. Lancet II:391–392
Miny P, Hammer P, Gerlach B, Tercanli S, Horst J, Holzgreve W, Eiben B (1991) Mosaicism and accuracy of prenatal cytogenetic diagnosis after chorionic villus sampling and placental biopsies. Prenat Diagn 11:581–589
Pinkel D, Landegent J, Collins C, Fuscoe J, Segraves R, Lucas J, Gray J (1988) Fluorescence in situ hybridization with human chromosome-specific libraries: detection of trisomy 21 and translocations of chromosome 4. Proc Natl Acad Sci USA 85:9138–9142
Schwinger E, Seidl E, Klink F, Rehder H (1989) Chromosomal mosaicism of the placenta. A cause of developmental failure of the fetus. Prenat Diagn 9:639–647
Simoni G, Brambatti B, Danesino C, Rossella F, Terzoli BL, Ferrari M, Fraccaro M (1983) Efficient direct chromosome analyses and enzyme determinations from chorionic villi samples in the first trimester of pregnancy. Hum Genet 63:239–257
Simpson JL (1990) Incidence and timing of pregnancy losses: relevance to evaluating safety of early prenatal diagnosis. J Med Genet 35:165–173
Teshima LE, Kalousek DK, Vekemans MJJ, Markovic V, Cox DM, Dalliare L, Gagne R, Lin CC, Ray M, Sergovich FR, Uchida IA, Wang H, Tomkins DJ (1992) Chromosome mosaicism in CVS and amniocentesis samples. Prenat Diagn 12:443–466
Wenger SL, Boone LY, Steele MW (1990) Mosaicism in Pallister i(12p) syndrome. Am J Med Genet 35:523–525
Wirtz A, Seidel H, Brusis E, Murken J (1988) Another false-nega-tive finding on placental sampling. Prenat Diagn 8:321
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Harrison, K.J., Barrett, I.J., Lomax, B.L. et al. Detection of confined placental mosaicism in trisomy 18 conceptions using interphase cytogenetic analysis. Hum Genet 92, 353–358 (1993). https://doi.org/10.1007/BF01247334
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF01247334