Preimplantation Genetic Diagnosis for Couples at High Risk of Down Syndrome Pregnancy Owing to Parental Translocation or Mosaicism

Overview

Journal J Med Genet

Specialty Genetics

Date 1999 Feb 9

PMID 9950365

Citations 10

Authors

C M Conn

J Cozzi

J C Harper

R M Winston

J D Delhanty

Affiliations

Soon will be listed here.

Abstract

The population risk for trisomy 21 is 1 in 700 births but some couples are at a much higher risk owing to parental translocation or mosaicism. We report on the first attempt to carry out preimplantation genetic diagnosis for two such couples using cleavage stage embryo biopsy and dual colour FISH analysis. Each couple underwent two treatment cycles. Couple 1 (suspected gonadal mosaicism for trisomy 21) had two embryos normal for chromosome 21 transferred, but no pregnancy resulted; 64% (7/11) unfertilised oocytes/embryos showed chromosome 21 aneuploidy. Couple 2 (46,XX,t(6;21)(q13;q22.3)) had a single embryo transferred resulting in a biochemical pregnancy; 91% (10/11) oocytes/embryos showed chromosome 21 imbalance, most resulting from 3:1 segregation of this translocation at gametogenesis. The opportunity to test embryos before implantation enables the outcome of female meiosis to be studied for the first time and the recurrence risk for a Down syndrome pregnancy to be assessed.

Citing Articles

The Clinical Effectiveness of Preimplantation Genetic Diagnosis for Chromosomal Translocation Carriers: A Meta-analysis.

Mahdavi M, Sharafi S, Daniali S, Riahi R, Kheirollahi M Glob Med Genet. 2020; 7(1):14-21.

PMID: 32879919 PMC: 7410090. DOI: 10.1055/s-0040-1712455.

Characterization of a Rare Mosaicism in Autosomal Translocation of t(5;21) Using Conventional Cytogenetics and FISH Methods.

Omori Sarabi S, Karimzad Hagh J, Behrend C, Mohseni S, Dezfouli M, Rashidi S Iran Biomed J. 2019; 24(1):60-3.

PMID: 31301695 PMC: 6900479.

Inheritance of a Chromosome 3 and 21 Translocation in the Fetuses, with One also Having Trisomy 21, in Three Pregnancies in One Family.

Pazarbasi A, Demirhan O, Alptekin D, Ozgunen F, Ozpak L, Yilmaz M Balkan J Med Genet. 2014; 16(2):91-6.

PMID: 24778571 PMC: 4001423. DOI: 10.2478/bjmg-2013-0039.

A clinical appraisal of the genetic basis in unexplained male infertility.

Esteves S J Hum Reprod Sci. 2013; 6(3):176-82.

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A comprehensive review of genetics and genetic testing in azoospermia.

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References

Pangalos C, Talbot Jr C, Lewis J, Adelsberger P, Petersen M, Serre J . DNA polymorphism analysis in families with recurrence of free trisomy 21. Am J Hum Genet. 1992; 51(5):1015-27. PMC: 1682858. View

Zheng Y, Ferguson-Smith M, Warner J, FERGUSON-SMITH M, Sargent C, Carter N . Analysis of chromosome 21 copy number in uncultured amniocytes by fluorescence in situ hybridization using a cosmid contig. Prenat Diagn. 1992; 12(11):931-43. DOI: 10.1002/pd.1970121113. View

Lengauer C, Green E, Cremer T . Fluorescence in situ hybridization of YAC clones after Alu-PCR amplification. Genomics. 1992; 13(3):826-8. DOI: 10.1016/0888-7543(92)90160-t. View

Gnirke A, Barnes T, Patterson D, Schild D, Featherstone T, Olson M . Cloning and in vivo expression of the human GART gene using yeast artificial chromosomes. EMBO J. 1991; 10(7):1629-34. PMC: 452831. DOI: 10.1002/j.1460-2075.1991.tb07685.x. View

Hopman A, Ramaekers F, Raap A, Beck J, Devilee P, VAN DER PLOEG M . In situ hybridization as a tool to study numerical chromosome aberrations in solid bladder tumors. Histochemistry. 1988; 89(4):307-16. DOI: 10.1007/BF00500631. View

Hillier S, Afnan A, Margara R, Winston R . Superovulation strategy before in vitro fertilization. Clin Obstet Gynaecol. 1985; 12(3):687-723. View

Mikkelsen M, Stene J . Genetic counselling in Down's syndrome. Hum Hered. 1970; 20(5):457-64. DOI: 10.1159/000152346. View

Jalbert P, Sele B, Jalbert H . Reciprocal translocations: a way to predict the mode of imbalanced segregation by pachytene-diagram drawing. Hum Genet. 1980; 55(2):209-22. DOI: 10.1007/BF00291769. View

Harper J, Coonen E, Handyside A, Winston R, Hopman A, Delhanty J . Mosaicism of autosomes and sex chromosomes in morphologically normal, monospermic preimplantation human embryos. Prenat Diagn. 1995; 15(1):41-9. DOI: 10.1002/pd.1970150109. View

10.

Soloviev I, Yurov Y, Vorsanova S, Fayet F, Roizes G, Malet P . Prenatal diagnosis of trisomy 21 using interphase fluorescence in situ hybridization of post-replicated cells with site-specific cosmid and cosmid contig probes. Prenat Diagn. 1995; 15(3):237-48. DOI: 10.1002/pd.1970150307. View

11.

Davies A, Barber L, Bobrow M, Adinolfi M . FISH detection of trisomy 21 in interphase by the simultaneous use of two differentially labelled cosmid contigs. J Med Genet. 1994; 31(9):679-85. PMC: 1050076. DOI: 10.1136/jmg.31.9.679. View

12.

Griffin D, Handyside A, Harper J, Wilton L, Atkinson G, Soussis I . Clinical experience with preimplantation diagnosis of sex by dual fluorescent in situ hybridization. J Assist Reprod Genet. 1994; 11(3):132-43. DOI: 10.1007/BF02332090. View

13.

Robinson W, Binkert F, Bernasconi F, Lorda-Sanchez I, WERDER E, Schinzel A . Molecular studies of chromosomal mosaicism: relative frequency of chromosome gain or loss and possible role of cell selection. Am J Hum Genet. 1995; 56(2):444-51. PMC: 1801123. View

14.

James R, Klerkx A, Keighren M, Flockhart J, West J . Restricted distribution of tetraploid cells in mouse tetraploid<==>diploid chimaeras. Dev Biol. 1995; 167(1):213-26. DOI: 10.1006/dbio.1995.1018. View

15.

Almeida P, Bolton V . The relationship between chromosomal abnormalities in the human oocyte and fertilization in vitro. Hum Reprod. 1994; 9(2):343-6. DOI: 10.1093/oxfordjournals.humrep.a138505. View

16.

Harper J, Coonen E, Ramaekers F, Delhanty J, Handyside A, Winston R . Identification of the sex of human preimplantation embryos in two hours using an improved spreading method and fluorescent in-situ hybridization (FISH) using directly labelled probes. Hum Reprod. 1994; 9(4):721-4. DOI: 10.1093/oxfordjournals.humrep.a138577. View

17.

Munne S, Lee A, Rosenwaks Z, Grifo J, Cohen J . Diagnosis of major chromosome aneuploidies in human preimplantation embryos. Hum Reprod. 1993; 8(12):2185-91. DOI: 10.1093/oxfordjournals.humrep.a138001. View

18.

Benkhalifa M, Janny L, Vye P, Malet P, Boucher D, Menezo Y . Assessment of polyploidy in human morulae and blastocysts using co-culture and fluorescent in-situ hybridization. Hum Reprod. 1993; 8(6):895-902. DOI: 10.1093/oxfordjournals.humrep.a138162. View

19.

Delhanty J, Griffin D, Handyside A, Harper J, Atkinson G, Pieters M . Detection of aneuploidy and chromosomal mosaicism in human embryos during preimplantation sex determination by fluorescent in situ hybridisation, (FISH). Hum Mol Genet. 1993; 2(8):1183-5. DOI: 10.1093/hmg/2.8.1183. View

20.

van Steirteghem A, Nagy Z, Joris H, Liu J, Staessen C, Smitz J . High fertilization and implantation rates after intracytoplasmic sperm injection. Hum Reprod. 1993; 8(7):1061-6. DOI: 10.1093/oxfordjournals.humrep.a138192. View