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Non-invasive prenatal screening (NIPS or NIPT) using cell-free DNA has been widely adopted into clinical practice and is currently used to identify pregnancies that have an increased chance of chromosome conditions such as Down syndrome, Edwards syndrome and Patau syndrome.

Genome-wide NIPS is an advanced form of NIPS that is used to screen all 23 pairs of chromosomes. This test can identify whole extra or missing chromosomes, as well as partial deletions or duplications of chromosomes.

New research published by the Victorian Clinical Genetics Services (VCGS) demonstrated that genome-wide NIPS can be a sensitive and accurate non-invasive method to detect unbalanced translocations in pregnancy from couples with known reciprocal translocations. Unbalanced translocations in pregnancy may result in miscarriage, fetal anomalies, and birth defects.

What is an unbalanced reciprocal translocation?

Approximately 1 in 500 people have a balanced reciprocal translocation. This means there has been a two-way exchange of genetic material between two chromosomes. When the amount of genetic material is balanced, that is, no genetic material is lost or gained, there is no effect on the individual’s health; they are called a carrier.

However, carriers are at risk of passing on an unbalanced form of the chromosomal rearrangement at conception, resulting in genetic material being lost and/or gained. This can lead to poor fertility outcomes, recurrent miscarriages, or more rarely, the birth of a child with an intellectual disability and congenital malformations.

Currently, pregnant couples where one person is a known balanced reciprocal translocation carrier are offered invasive diagnostic procedures, such as chorionic villus sampling (CVS) or amniocentesis, which are used to diagnose unbalanced translocations. However many couples may hesitate or decline these procedures because of the associated, albeit low, miscarriage risk.

A sensitive and non-invasive screening option

VCGS is a leading genetics services provider, based at The Royal Children’s Hospital, Melbourne. Our experience indicates there is strong interest from couples seeking a non-invasive testing option for detecting unbalanced translocations during their pregnancy.

Research from VCGS, led by NIPS Group Leader Nicola Flowers, was recently published in Genetics in Medicine. This work demonstrated that genome-wide NIPS can provide a sensitive and accurate screening option for translocation carrier couples. These findings have been reiterated through analysis of over 240 samples, completed by VCGS since the original analysis work for this paper.

NIPS is an attractive alternative to CVS or amniocentesis, at it is done on maternal blood collected from a simple blood draw.

Clinical scientist and Head of the Reproductive Genetics division at VCGS Dr Mark Pertile said “This research arose out of requests from clinicians and translocation carrier couples seeking an alternative to invasive procedures for diagnosis. We adapted our genome-wide NIPS assay to meet this need”.

The VCGS NIPS team is also currently supervising a Master of Genetic Counselling research project which is looking to understand the patient experience of using NIPS to screen for unbalanced translocations. The research, conducted by student Marta Cifuentes Ochoa, has found that because of complex reproductive histories, including infertility and multiple miscarriages, couples prefer a non-invasive screening option. Participants were appreciative of this screening approach which was tailored to their specific needs and provided reassurance. “…It could be done fairly early, it was going to be really accurate [for the translocation analysis] in my case, so I could trust it… would give me almost a confirmation that everything was ok without having to do anything invasive…” said one participant.

Learn more about genome-wide NIPS at VCGS.

Paper citation: Flowers, N. J., et al. Genome-wide noninvasive prenatal screening for carriers of balanced reciprocal translocations. Genet Med 2020.

Note: Reciprocal translocation analysis using genome-wide NIPS may not be suitable for all couples. Prior assessment and approval for each translocation is required. Please contact the laboratory for an assessment. P: 1300 118 247