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Vineland adaptive behavior scale in a cohort of four ADNP syndrome patients implicates age-dependent developmental delays with increased impact of activities of daily living Universiteit Antwerpen
Activity-dependent neuroprotective protein (ADNP) is one of the lead genes in autism spectrum disorder/intellectual disability. Heterozygous, de novo ADNP mutations cause the ADNP syndrome. Here, to evaluate natural history of the syndrome, mothers of two ADNP syndrome boys aged 6 and a half and two adults aged 27 years (man and woman) were subjected to Vineland III questionnaire assessing adaptive behavior. The boys were assessed again about 2 ...
Expanding the phenotype of B3GALNT2-related disorders Universiteit Antwerpen Universiteit Gent
Dystroglycanopathies are a group of congenital muscular dystrophies (CMDs) that include a broad phenotypic spectrum ranging from late-onset limb-girdle muscular dystrophy to severe muscle-eye-brain disease, Walker-Warburg syndrome, and Fukuyama congenital muscular dystrophy. In addition to clinical heterogeneity, CMDs are characterized by genetic heterogeneity. To date, 18 genes have been associated with CMDs. One of them is B3GALNT2, which ...
Towards kinase inhibitor therapies for Fragile X syndrome Universiteit Antwerpen
Absence of the Fragile X Messenger Ribonucleoprotein 1 (FMRP) causes autism spectrum disorders and intellectual disability, commonly referred to as the Fragile X syndrome. FMRP is a negative regulator of protein translation and is essential for neuronal development and synapse formation. FMRP is a target for several post-translational modifications (PTMs) such as phosphorylation and methylation, which tightly regulate its cellular functions. ...
Non-Mendelian inheritance patterns and extreme deviation rates of CGG repeats in autism Universiteit Antwerpen
As expansions of CGG short tandem repeats (STRs) are established as the genetic etiology of many neurodevelopmental disorders, we aimed to elucidate the inheritance patterns and role of CGG STRs in autism-spectrum disorder (ASD). By genotyping 6063 CGG STR loci in a large cohort of trios and quads with an ASD-affected proband, we determined an unprecedented rate of CGG repeat length deviation across a single generation. Although the concept of ...
Therapeutic potential of GABA(A) receptor subunit expression abnormalities in fragile X syndrome Universiteit Antwerpen
Introduction: Many studies have reported brain region and age-dependent alterations in the expression of several subunits of the GABA(A) receptor in Fmr1 KO mice. GABA(A) receptors are located synaptic and extrasynaptic with differential subunit compositions and characteristics. Interestingly, the activity of many subunits of the GABA(A) receptor is amendable by differential pharmacological treatment. Areas Covered: The purpose of this review is ...
Abundancy of polymorphic CGG repeats in the human genome suggest a broad involvement in neurological disease Universiteit Antwerpen
Expanded CGG-repeats have been linked to neurodevelopmental and neurodegenerative disorders, including the fragile X syndrome and fragile X-associated tremor/ataxia syndrome (FXTAS). We hypothesized that as of yet uncharacterised CGG-repeat expansions within the genome contribute to human disease. To catalogue the CGG-repeats, 544 human whole genomes were analyzed. In total, 6101 unique CGG-repeats were detected of which more than 93% were ...
Discovery of autism/intellectual disability somatic mutations in Alzheimer's brains Universiteit Antwerpen
With Alzheimer’s disease (AD) exhibiting reduced ability of neural stem cell renewal, we hypothesized that de novo mutations controlling embryonic development, in the form of brain somatic mutations instigate the disease. A leading gene presenting heterozygous dominant de novo autism-intellectual disabilities (ID) causing mutations is activity-dependent neuroprotective protein (ADNP), with intact ADNP protecting against AD-tauopathy. We ...
JARID2 haploinsufficiency is associated with a clinically distinct neurodevelopmental syndrome Universiteit Antwerpen
Purpose JARID2, located on chromosome 6p22.3, is a regulator of histone methyltransferase complexes that is expressed in human neurons. So far, 13 individuals sharing clinical features including intellectual disability (ID) were reported with de novo heterozygous deletions in 6p22–p24 encompassing the full length JARID2 gene (OMIM 601594). However, all published individuals to date have a deletion of at least one other adjoining gene, making it ...
A contemporary view on the molecular basis of neurodevelopmental disorders Universiteit Antwerpen
Genetic variation is a major contributor to the pathogenesis of neurodevelopmental disorders (NDDs). These disorders are defined by a disturbed development of the central nervous system resulting in deficits in personal, social and cognitive functioning that manifest during the early years of life. The NDD group encompasses intellectual disability (ID), autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), ...