Publications
A syndrome of short stature, microcephaly and speech delay is associated with duplications reciprocal to the common Sotos syndrome deletion Vrije Universiteit Brussel KU Leuven
Genomic rearrangements are an increasingly recognized mechanism of human phenotypic variation and susceptibility to disease. Sotos syndrome is characterized by overgrowth, macrocephaly, developmental delay and advanced osseous maturation. Haploinsufficiency of NSD1, caused by inactivating point mutations or deletion copy number variants, is the only known cause of Sotos syndrome. A recurrent 2 Mb deletion has been described with variable ...
Brain endothelial TAK1 and NEMO safeguard the neurovascular unit Vrije Universiteit Brussel KU Leuven
Inactivating mutations of the NF-κB essential modulator (NEMO), a key component of NF-κB signaling, cause the genetic disease incontinentia pigmenti (IP). This leads to severe neurological symptoms, but the mechanisms underlying brain involvement were unclear. Here, we show that selectively deleting Nemo or the upstream kinase Tak1 in brain endothelial cells resulted in death of endothelial cells, a rarefaction of brain microvessels, cerebral ...
Interaction of glibenclamide and metformin at the level of translation in pancreatic β cells Vrije Universiteit Brussel
Sulfonylurea and metformin are used in the treatment of diabetes. Their chronic effects on β cells are not well known. We have shown that sustained exposure of rat β cells to glibenclamide increased their protein synthesis activity, while metformin caused an inhibition. The effect of glibenclamide was attributed to an activation of translation factors. This study examines whether both drugs interact at the level of protein translation in β ...
Relative contribution of simple mutations vs. copy number variations in five Parkinson disease genes in the Belgian population Vrije Universiteit Brussel University of Antwerp
The relative contribution of simple mutations and copy number variations (CNVs) in SNCA, PARK2, PINK1, PARK7, and LRRK2 to the genetic etiology of Parkinson disease (PD) is still unclear because most studies did not completely analyze each gene. In a large group of Belgian PD patients (N = 310) and control individuals (N = 270), we determined the mutation frequency of both simple mutations and CNVs in these five PD genes, using direct ...
Improvement of biochemical and behavioral defects in the Niemann-Pick type A mouse by intraventricular infusion of MARCKS Vrije Universiteit Brussel KU Leuven
Niemann-Pick disease type A (NPDA) is a fatal disease due to mutations in the acid sphingomyelinase (ASM) gene, which triggers the abnormal accumulation of sphingomyelin (SM) in lysosomes and the plasma membrane of mutant cells. Although the disease affects multiple organs, the impact on the brain is the most invalidating feature. The mechanisms responsible for the cognitive deficit characteristic of this condition are only partially ...
Generation and diagnostic valorisation of monoclonal antibodies for human protein tau KU Leuven
Loss, Gain and Altered Function of GlyR α2 Subunit Mutations in Neurodevelopmental Disorders Vrije Universiteit Brussel
Glycine receptors (GlyRs) containing the α2 subunit govern cell fate, neuronal migration and synaptogenesis in the developing cortex and spinal cord. Rare missense variants and microdeletions in the X-linked GlyR α2 subunit gene (GLRA2) have been associated with human autism spectrum disorder (ASD), where they typically cause a loss-of-function via protein truncation, reduced cell-surface trafficking and/or reduced glycine sensitivity (e.g., ...