Genome-wide analysis now also possible for intended parents with a new genetic disorder

31 August 2021
At UZ Leuven it is now possible for intended parents to screen an embryo for a genetic disorder that did not previously occur in the family with one single test. Researchers at the Leuven centre for human genetics developed an all-in-one test for monitor embryos for a de novo genetic disorder.

It's a test that makes it possible to do both a targeted and genome-wide analysis of the embryos of a parent with a de novo variant. It enables physicians to look at the disorder carried by the parent as well as potential other disorders in the embryo's genome. It is the first time in Belgium it's been possible to do genome-wide testing for de novo disorders with one single test.  

Couples with an increased risk of having a child with a serious genetic disorder, can choose for a pre-implant genetic test (PGT). After producing embryos via in vitro fertilisation (IVF) specialists perform a genetic analysis to detect serious hereditary disorders, such as genetic breast cancer or kidney disease. Only the embryos without those genetic disorders will be inserted in the uterus. That way couples can avoid a pregnancy with the baby inheriting the disorder. 

This genetic analysis of hereditary disorders is done on the basis of DNA material of other family members of the parents. At the Leuvense centre for human genetics, geneticists are not only looking for the genetic disorder itself, but they are also analysing the embryo genome-wide. That way they're also ‘fishing’ for other possible disorders in the embryo, such as Down syndrome or other genetic diseases. 

No comparative material

Until recently, genome-wide tracing of diseases was not possible for people with a de novo variant, a genetic mutation that until then had never occurred in the family history of that person. For a de novo variant there is no comparative material of the family to perform the genetic analysis on. A de novo variant in a parent has however a 50 procent risk of passing on the disease to the baby. The most common diseases you can pass on to a child without it having occurred previously in the family, are e.g. neurofibromatosis, polycystic kidney diseases or a kidney disease named Alport syndrome. 

Researchers of the Leuven centre for human genetics have now developed a test which makes it possible to do a targeted and genome-wide analysis of the embryo of a parent with a de novo genetic disease. This is done on the basis of a comparison of the DNA of the grandparents of the embryo on the side of the parent carrying the disease. One of the grandparent has the same DNA as the intended parent with the de novo variant, but without the genetic mutation causing the disease. By comparing the two DNA patterns, the grandparents' information can be used on the basis of other characteristices that go hand-in-hand with the mutation. This allows the researchers to determine whether the mutation causing the disease originates from the maternal or paternal side of the family. 

To have all info in one test, about the disease carried by the parent as well as the embryo's whole genome, is a big step forward
Eftychia Dimitriadou

Less time to get a consultation

Until recently, parents in that situation could take several separate tests that were time-consuming and expensive. Now they can get to all genetic material with just one test. It's the first time that a genome-wide analysis is done for de novo variants with the help of one single test. UZ Leuven is the only Belgian hospital to provide this. 

Eftychia Dimitriadou, specialist reproductive genetics at UZ Leuven: “For people with a de novo genetic disease there were long waiting times. It could take months, years even, before they could come to a consultation for an implantation of tested embryos. To have all info in one test, about the disease carried by the parent as well as about the embryo's whole genome, is a big step forward.”

Just like other pre-implanation tests, the test is reimbursed by NIHDI (RIZIV). Since the test has been in use, it has resulted in six pregnancies and the birth of three babies. On Tuesday 31 August dr. Dimitriadou presented her results at the conference of the European Society of Human Genetics.

Read the press release of the European Society of Human Genetics.

Last edit: 1 September 2021