Preimplantation Genetic Testing-Structural Rearrangements (PGT-SR)
Preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) is a genetic test available for carriers of balanced chromosome rearrangement including reciprocal translocations, Robertsonian translocations, and inversions.
1. Reciprocal translocations: Pieces of two chromosomes that have broken off and switched places; it is “balanced” because there is no extra or missing chromosome material (Figure 1). About 80% of resulting embryos will contain an incorrect amount of genetic material if one parent is a carrier of a reciprocal translocation.
Figure 1 Reciprocal translocations
About 80% of resulting embryos will contain an incorrect amount of genetic material if one parent is a carrier of a reciprocal translocation (Figure 2).
A carrier of a balanced translocation may produce offspring with normal chromosomal complements or balanced non-carrier (A), offspring who are also carriers of the balanced rearrangement (B), or offspring with unbalanced translocations (C).
2. Robertsonian translocations: This happens between two chromosomes with one long arm and one very short arm (chromosome 13, 14, 15, 21, 22). The short arms are lost, and the long arms fuse to form one large chromosome, giving an overall chromosome count of 45 instead of 46 (Figure 3).
Figure 3 Robertsonian translocations
This can cause conditions including Translocation Down syndrome (Trisomy 21) (Figure 4), Patau syndrome (Trisomy 13), or uniparental disomy (UPD). Examples of diseases associated with UPD include Prader-Willi syndrome, Angelman syndrome and Beckwith-Wiedemann syndrome). This figure shows Translocation Down syndrome. There is a Robertsonian translocation involving chromosomes 21 and 14, which has been inherited from a parent.
Robertsonian translocations occur in approximately 0.1% in the general population, 1.1% in patients with recurrent pregnancy loss (RPL), and 3% in infertile men. Chromosome studies should be obtained on both parents if their offspring is found to have a Robertsonian translocation. In general, the recurrence risk is 15 percent if carried by the mother and 2 percent if carried by the father.
3. Inversions: Part of a chromosome is turned upside down and reinserted back into the chromosome.
A pericentric inversion includes the centromere in the inverted segment, while a paracentric inversion does not. People with an inversion may create embryos with deleted or duplicated segments of chromosomes.
5 Steps to perform the PGT-SR