The Centre for Medical Genetics (CMG) is one of the spearheads of the UZ Brussel and one of the eight genetic centres in Belgium. Through the efficient operation of its clinic and laboratory, the CMG aims to offer a high-quality care programme to its patients. Next to its extensive diagnostic activities, CMG also conducts clinical research covering a broad spectrum of topics within medical genetics, including reproductive genetics, pre-implantation genetic testing, oncogenetics, cytogenetics, cardiogenetics, and rare genetic diseases. Its staff consists of a large team of experts in clinical genetics, molecular biology, genetic counselling, … offering broad expertise concerning human genetic research.
The CMG is equipped with a high-tech diagnostic laboratory (ISO 15189:2022) including state-of-the-art next-generation sequencing technologies (both short and long range). Through its intensive collaboration with the BRIGHTcore facility, CMG share a team of bioinformatics for the analyses of (epi)genome, transcriptome, and other large genetic datasets. Using its expertise and technological capacity, CMG often collaborates with other VUB research groups, Brussels IVF and national and international groups.
For the most recent updates on the CMG's research activities, please visit our LinkedIn page: https://www.linkedin.com/company/centrum-voor-medische-genetica-uz-brussel.
Research Projects
Pre-implantation Genetic Testing (PGT)
Pre-implantation Genetic Testing (PGT) is a pioneering technique where parents who carry a pathogenic genetic variation (dominant or recessive) can avoid passing it on to their offspring. After mapping the variant, an ICSI cycle is initiated at the Brussels IVF centre. The fertilised eggs are cultured in the laboratory after which a biopsy is taken from the early-stage embryo for genetic testing without effect on further development. These samples are then transferred to the CMG where genetic testing determines whether the embryo has inherited the genetic variant so that only embryos without variant can be implanted in the uterus. PGT can be consulted for several genetic disorders such as monogenic disorders (PGT-M), structural rearrangements (PGT-SR) and aneuploidies (PGT-A), and special cases such as HLA compatibility.
The PGT clinic at UZ Brussel was one of the first of its kind in Europe with the first cycles started in the early 1990s. Furthermore, 1.000s of children born from a PGT cycle are followed up in time. Therefore, to this day, the UZ Brussel PGT clinic is one of the leading centres on the continent.
Currently several studies in the field of PGT are being conducted at CMG including:
- Children born after in vitro maturation of oocytes (IVM) to mothers with PCOS: are they at risk for cardiometabolic morbidity and/or vascular dysfunction?
- ART-related epigenetic instability and endothelial function: a pilot study in 8-year-old children born after Pre-implantation Genetic Testing and their spontaneously conceived siblings.
Oncogenetics
Oncogenetics focusses on two pillars of analyses: somatic tumourprofiling and hereditary cancer predisposition. Somatic tumourprofiling is performed on both solid and haematological malignancies to identify tumour specific genetic variants, also gene fusions and exon skippings can be detected. With these analyses, genetic variants can be found which can have a prognostic meaning or enable certain, directed therapies. For cancer predisposition, blood is analysed for the detection of (likely) pathogenic germline variants linked to familial breast, ovarian, and colorectal cancer.
Currently several studies in the field of Oncogenetics are being conducted at CMG including:
- Functional transcriptomics as fast track to resolve the biological and clinical impact of variants of unknown significance in comprehensive molecular tumour profiling.
- Unravelling DNA variants of unknown significance: A promising path to further diagnosis, prognosis, and targeted therapies in cancer patients.
CLARITY
The CLARITY (Clarifying the functional effect of genetic variants of unknown significance for improved patient therapy) program was established to better characterise genetic variants with unknown effect. Such variants are frequently found in genetic tests (hereditary diseases, cancer predisposition, pre-implantation genetic testing, tumour profiling, ...) and leave the patient with an incompletely answered genetic question. Therefore, within the CLARITY program, several studies are being conducted to elucidate these unknown genetic variants:
- Deciphering the effect of VUS on splicing: Splice Site Assay for accurate diagnosis, prognosis, and treatment methods for genetic disorders.
- Unravelling DNA variants of unknown significance: A promising path to further diagnosis, prognosis, and targeted therapies in cancer patients.
Rare Diseases
Rare Diseases is an umbrella term for some 7,000 conditions such as Ehlers-Danlos syndrome, acromegaly, sickle cell anaemia, immune deficiencies, syndromes with dysmorphologies… Despite being "rare", an estimated 500,000 people in Belgium suffer from a rare disease, of whom >70% have a genetic cause.
Currently several studies in the field of Rare Diseases are being conducted at CMG including:
- Unravelling the molecular aetiology of Pompe disease.
- Combining exome and transcriptome data to unravel the genetic basis of lissencephalies.
- A multi-omics approach to improve the diagnosis of genetic disorders.
- Working patient centred in the context of cardiogenetics: recommendations towards an improved care pathway for patients with inherited conditions.
- Prenatal genetic odyssey for congenital malformations: Investigation of genes involved in malformations of cortical development.
