Preimplantation genetic diagnosis of chromosome balance in embryos from a patient with a balanced reciprocal translocation

Abstract

Duplications or deletions are present in a high percentage of the gametes produced by individuals carrying balanced translocations. Preimplantation genetic diagnosis was used to examine chromosome balance in embryos from a patient having a reciprocal translocation within the short arms of chromosomes 5 and 8 (46,XX,t(5;8)(p13;p23)). This woman has two sisters with the translocation unbalanced, resulting in a partial trisomy for chromosome 5 and partial monosomy for chromosome 8 (46,XX,-8, +der(8)t(5;8)(p13;p23)) with associated mental retardation and physical abnormalities. The patient and her husband desired to have children without the abnormal chromosome balance and wished to reduce the likelihood of spontaneous abortion or need for therapeutic abortion. Fluorescence in-situ hybridization (FISH) probes for the alpha-satellite region of chromosome 8 and for a region on the short arm of chromosome 5 (5p15.2) were tested initially on lymphocytes from the patient and her sisters. The hybridization signal for chromosome 5 was detected in the expected two copies for the patient and three copies for the sisters in 87% of the cells. Two hybridization signals for chromosome 8 were detected in 96% of the cells from all individuals. Additional probe testing was done using blastomeres from polyspermic embryos. The couple then proceeded with a stimulated in-vitro fertilization (IVF) cycle and biopsies were done on 13 embryos at the 7-10-cell stage using a method of zona drilling and fluid displacement. Diagnosis was possible on at least one blastomere for nine embryos. Three embryos had nuclei with three hybridization signals for chromosome 5, three had fewer than two signals for one or both chromosomes, one was mosaic, and two had two signals for each chromosome. The latter were transferred to the patient, but pregnancy was not achieved. The results demonstrate that preimplantation genetic diagnosis for patients with reciprocal translocations can be used to identify embryos having normal chromosome balance. The potential advantages and limitations of this approach are discussed.

Benefits and drawbacks of preimplantation genetic diagnosis (PGD) for reciprocal translocations: lessons from a prospective cohort study

“…The median number of eggs collected was 13 (range 4-39) and the median number of embryos biopsied was 6 (range [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. In our study the number of oocytes was not an important predictor for a live-birth pregnancy (OR 1.0, 95% CI 0.92-1.10, P ¼ 0.960).…”

“…5,6 Some approaches allow discrimination between normal and heterozygote chromosome complements, as well as detecting abnormal copy number for the translocation segments. [7][8][9] However, the most commonly used methodology of locus-specific probes applied to interphase nuclei from cleavage stage blastomeres, [10][11][12][13][14][15][16] or cells sampled from the trophectoderm, 17 will not differentiate between normal and heterozygote chromosome complements unless probes are designed to flank closely or span the breakpoints. 18 Guy's and St Thomas' Centre for PGD has undertaken 319 biopsy cycles with genetic testing for 171 couples with reciprocal translocations, which has resulted in the delivery of 85 live-born offspring.…”

The importance of aneuploidy screening in reciprocal translocation carriers

“…Different strategies have been used for this purpose. (a) The use of translocation-specific fluorescence in-situ hybridisation (FISH) probes on individual blastomeres has been consistently successful for the detection of the products of both Robertsonian (Rob) and reciprocal translocations (Conn et al 1998, Munné et al 1998, Pierce et al 1998, Van Assche et al 1999. (b) Blastomere biopsy followed by blastomere fusion with mouse zygotes, which has been described as a method for obtaining metaphase chromosomes from individual human blastomeres (Verlinsky & Evsikov 1999, Willadsen et al 1999).…”

A rare chromosomal abnormality inherited from the mother in a boy conceived after intracytoplasmic sperm injection: a case report

“…Theoretically, a preimplantation genetic diagnosis could have been made if the mother was known to be a translocation carrier. In such cases, a polar body biopsy can reveal genetic anomalies as an alternative to blastomere biopsy [8]. Fig.…”