The study, published in Europe’s foremost reproductive medicine journal Human Reproduction, was done by researchers at the Center for Human Genetics, University Hospital Leuven (Belgium). The chief authors were Joris Vermeesch, coordinator of the Genomics Core and head of Constitutional Cytogenetics at the center, and Evelyne Vanneste, a doctoral student.
The scientists performed their study on three pregnant women whose embryos had not yet implanted in their wombs and who carried microdeletions for either neurofibromatosis type 1 (NF1) or Von Hippel-Lindau disease (VHL). If children had been born from embryos with these defects, they would have eventually developed a devastating syndrome characterized by tumors of the central nervous system and other severe afflictions. The conditions are caused by mutations or microdeletions in the NF1 or VHL genes, both of which suppress tumor growth.
The overall process pursued by the doctors is known as preimplantation genetic diagnosis (PGD). To obtain their embryonic diagnoses, they developed biochemical probes that identified dysfunctional NF1 and VHL genes. As a result of the researchers’ efforts, the woman with the VHL mutation gave birth to healthy twins from embryos selected using the microdeletion-identification technique called fluorescent in situ hybridization (FISH).
The work by Vermeesch and Vanneste opens the door to assaying chromosomes for microdeletions in patients with many genetic disorders beyond the two cancer-predisposition syndromes focused on in their study.
“It is becoming clear that genomic disorders caused by microdeletions … are much more frequent than previously thought,” Vermeesch said. “The techniques we have used in this study will help a wide range of microdeletion carriers.”
Vanneste explained that although they had to make biochemical FISH probes specific to each woman, the NF1 microdeletions found were inclined to occur again. “Therefore,” she said, “most NF1 patients with a deletion carry the same deletion and our FISH PGD conditions can be rapidly replicated and reused in other deletion carriers.
“It seems likely that the number of families that can benefit from FISH PGD will increase in years to come, and we are continuing to help more families using this approach. However, for each condition a new probe has to be made. This is time-consuming, but we are currently developing tools to identify all similar genetic imbalances with a single technology.”