Koen L.I. van Gassen
A5041388991- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Neuroscience and Neuropharmacology Research
- Epilepsy research and treatment
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Cellular transport and secretion
- Ion channel regulation and function
- Metabolism and Genetic Disorders
- RNA and protein synthesis mechanisms
- Mitochondrial Function and Pathology
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Congenital heart defects research
- RNA regulation and disease
- Cancer-related gene regulation
- Amino Acid Enzymes and Metabolism
- Erythrocyte Function and Pathophysiology
- Protein Tyrosine Phosphatases
- Genetic Neurodegenerative Diseases
- Neurogenetic and Muscular Disorders Research
- Drug Transport and Resistance Mechanisms
- Chromatin Remodeling and Cancer
University Medical Center Utrecht
2016-2025
Utrecht University
2007-2024
Heidelberg University
2018-2024
University Hospital Heidelberg
2018-2024
Wilhelmina Children's Hospital
2018-2024
Maastricht University
2021-2023
Cancer Genomics Centre
2020
Hertie Institute for Clinical Brain Research
2017
University of Southern Denmark
2017
University of Tübingen
2017
The advent of massive parallel sequencing is rapidly changing the strategies employed for genetic diagnosis and research rare diseases that involve a large number genes. So far it not clear whether these approaches perform significantly better than conventional single gene testing as requested by clinicians. current yield this traditional diagnostic approach depends on complex factors include gene-specific phenotype traits, relative frequency involvement specific To gauge impact paradigm...
Spastic paraplegia type 7 is an autosomal recessive neurodegenerative disorder mainly characterized by progressive bilateral lower limb spasticity and referred to as a form of hereditary spastic paraplegia. Additional disease features may also be observed part more complex phenotype. Many different mutations have already been identified, but no genotype–phenotype correlations found so far. From total almost 800 patients for testing, we identified 60 with in the SPG7 gene. We 14 previously...
The transcription factor BCL11B is essential for development of the nervous and immune system, Bcl11b deficiency results in structural brain defects, reduced learning capacity, impaired cell mice. However, precise role humans largely unexplored, except a single patient with missense mutation, affected by multisystem anomalies profound deficiency. Using massively parallel sequencing we identified 13 patients bearing heterozygous germline alterations BCL11B. Notably, all them are global...
Here we report inherited dysregulation of protein phosphatase activity as a cause intellectual disability (ID). De novo missense mutations in 2 subunits serine/threonine (Ser/Thr) 2A (PP2A) were identified 16 individuals with mild to severe ID, long-lasting hypotonia, epileptic susceptibility, frontal bossing, hypertelorism, and downslanting palpebral fissures. PP2A comprises catalytic (C), scaffolding (A), regulatory (B) that determine subcellular anchoring, substrate specificity,...
<h3>Objective:</h3> To examine the role of mutations in <i>GABRB3</i> encoding β<sub>3</sub> subunit GABA<sub>A</sub> receptor individual patients with epilepsy regard to causality, spectrum genetic variants, their pathophysiology, and associated phenotypes. <h3>Methods:</h3> We performed massive parallel sequencing 416 a range epileptic encephalopathies childhood-onset epilepsies recruited additional from other research diagnostic programs. <h3>Results:</h3> identified 22 heterozygous...
Chromatin remodeling is of crucial importance during brain development. Pathogenic alterations several chromatin ATPases have been implicated in neurodevelopmental disorders. We describe an index case with a de novo missense mutation CHD3, identified whole genome sequencing cohort children rare speech To gain comprehensive view features associated disruption this gene, we use genotype-driven approach, collecting and characterizing 35 individuals CHD3 mutations overlapping phenotypes. Most...
With the increasing number of genomic sequencing studies, hundreds genes have been implicated in neurodevelopmental disorders (NDDs). The rate gene discovery far outpaces our understanding genotype-phenotype correlations, with clinical characterization remaining a bottleneck for NDDs. Most disease-associated Mendelian are members families, and we hypothesize that those related molecular function share presentations.We tested hypothesis by considering families multiple an enrichment de novo...
Abstract CSMD1 ( Cub and Sushi Multiple Domains 1 ) is a well-recognized regulator of the complement cascade, an important component innate immune response. highly expressed in central nervous system (CNS) where emergent functions pathway modulate neural development synaptic activity. While genetic risk factor for neuropsychiatric disorders, role neurodevelopmental disorders unclear. Through international variant sharing, we identified inherited biallelic variants eight individuals from six...
MDH2 encodes mitochondrial malate dehydrogenase (MDH), which is essential for the conversion of to oxaloacetate as part proper functioning Krebs cycle. We report bi-allelic pathogenic mutations in three unrelated subjects presenting with early-onset generalized hypotonia, psychomotor delay, refractory epilepsy, and elevated lactate blood cerebrospinal fluid. Functional studies fibroblasts from affected showed both an apparently complete loss levels enzymatic activity close null. Metabolomics...