A5047534273- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- Genetic Neurodegenerative Diseases
- Cell Adhesion Molecules Research
- Hedgehog Signaling Pathway Studies
- ATP Synthase and ATPases Research
- Ion channel regulation and function
- Platelet Disorders and Treatments
- Adipose Tissue and Metabolism
- Genomic variations and chromosomal abnormalities
- Cardiomyopathy and Myosin Studies
- Connective tissue disorders research
- Epigenetics and DNA Methylation
- DNA Repair Mechanisms
- RNA modifications and cancer
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Genomics and Rare Diseases
- Molecular Biology Techniques and Applications
- Renal and related cancers
- Congenital heart defects research
- Cancer and Skin Lesions
- Metabolomics and Mass Spectrometry Studies
- Genetic and rare skin diseases.
- Hereditary Neurological Disorders
- Prenatal Screening and Diagnostics
Maastricht University Medical Centre
2006-2024
Maastricht University
2014-2024
Medisch Centrum Haaglanden
2018-2023
Radboud University Nijmegen
1989-2019
Catharina Ziekenhuis
2019
National Research Tomsk State University
2018
Genomics (United Kingdom)
2017
Aging Community Coordinated Enterprises and Supportive Services (United States)
2014
Access to Wholistic and Productive Living Institute
2014
Erasmus MC
2014
Benign familial hematuria (BFH) is characterized by autosomal dominant inheritance, thinning of the glomerular basement membrane (GBM) and normal renal function. It frequent in patients with persistent microscopic hematuria, but cannot be clinically differentiated from initial stages Alport syndrome, a severe GBM disorder which progresses to failure. We present here linkage benign COL4A3 COL4A4 genes at 2q35-37 (Zmax = 3.58 theta 0.0). Subsequently, glycine glutamic acid substitution was...
<h3>Background</h3> Alport syndrome is a clinically heterogeneous, progressive nephropathy caused by mutations in collagen IV genes, namely <i>COL4A3</i> and <i>COL4A4</i> on chromosome 2 <i>COL4A5</i> X. The wide phenotypic variability the presence of incomplete penetrance suggest that simple Mendelian model cannot completely explain genetic control this disease. Therefore, we explored possibility under digenic control. <h3>Methods</h3> Using massively parallel sequencing, identified 11...
Myotonic dystrophy type 1 (DM1) is one of the most variable inherited human disorders. It characterized by involvement multiple tissues and caused expansion a highly unstable CTG repeat. Variation in disease severity partially accounted for number repeats inherited. However, basis tissue-specific symptoms unknown. We have determined that an unusual Dutch family co-segregating DM1, Charcot-Marie-Tooth neuropathy, encephalopathic attacks early hearing loss, carries complex variant repeat at...
Phenotypic heterogeneity and incomplete penetrance are common in patients with hypertrophic cardiomyopathy (HCM). We aim to improve the understanding genotype–phenotype correlations HCM, particularly contribution of an MYL2 founder mutation risk factors left ventricular remodelling. analysed 14 HCM families whom 38 family members share c.64G > A [p.(Glu22Lys)] a haplotype. In this unique cohort, we investigated influencing phenotypic outcome addition primary mutation. The alone showed benign...
Five patients with diminished activity of complex III the mitochondrial respiratory chain have been screened for mutations in cytochrome b (cyt b) gene. In 1 patient, a young boy an akinetic rigid syndrome and encephalomyopathy lactic acidosis stroke-like episodes (MELAS), novel 4-base pair deletion was identified. This mutation this highly conserved gene is considered to be pathogenic since it heteroplasmic frame shift predicted lead truncated protein.
Five patients with diminished activity of complex III the mitochondrial respiratory chain have been screened for mutations in cytochrome b (cyt b) gene. In 1 patient, a young boy an akinetic rigid syndrome and encephalomyopathy lactic acidosis stroke-like episodes (MELAS), novel 4–base pair deletion was identified. This mutation this highly conserved gene is considered to be pathogenic since it heteroplasmic frame shift predicted lead truncated protein. Ann Neurol 1999;45:130–133
The functionality of the p53-mediated pathway, activated in response to DNA damage, has been assessed primary fibroblast cell cultures and Epstein-Barr virus-transformed lymphoblastoid lines derived from Nijmegen breakage syndrome (NBS) patients. This autosomal recessive disease is characterized by microcephaly, growth mental retardation, chromosomal instability, radiosensitivity, high cancer incidence. recent mapping NBS gene chromosome 8q21 demonstrates that genetically distinct ataxia...
Several studies show an association of a guanine for adenine substitution (A-->G) at position 3243 in mitochondrial DNA (mtDNA) with recently recognized diabetic subtype designated maternally inherited diabetes and deafness (MIDD). This mutation shows heterogeneity its phenotypic expression as is apparent from several other syndromes. Screening the 3243A-->G mtDNA was performed those patients attending Leiden University Hospital diabetics clinic who had history diabetes, sensorineural...
Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system in which macrophages and microglia play role. Foamy microglia, containing degenerated myelin, are abundantly found active multiple lesions. Recent studies have described an altered macrophage phenotype after myelin internalization. However, it unclear by mechanisms affects how this can influence lesion progression. Here we demonstrate, using genome wide gene expression analysis, that...
Cyclooxygenase-2 (COX-2) is frequently over-expressed in primary breast cancer. In transgenic cancer models, over-expression of COX-2 leads to tumour formation while inhibition exerts anti-tumour effects cell lines. To further determine the effect cancer, we aimed identify transcriptional changes tissues patients treated with selective inhibitor celecoxib.In a single-centre double-blind phase II study, thirty-seven were randomised receive either pre-operative celecoxib (400 mg) twice daily...
About 2-7% of familial cardiomyopathy cases are caused by a mutation in the gene encoding cardiac troponin I (TNNI3). The related clinical phenotype is usually severe with early onset. Here we report on all currently known mutations Dutch population and compared these those described literature.TheTNNI3 was screened for coding exons flanking intronic sequences large cohort patients. All index carrying TNNI3 that this study underwent extensive cardiological evaluation were listed their postal...
High mitochondrial DNA (mtDNA) copy numbers are essential for oogenesis and embryogenesis correlate with fertility of oocytes viability embryos. To understand the pathology mechanisms associated low mtDNA numbers, we knocked down transcription factor A (tfam), a regulator replication, during early zebrafish development. Reduction tfam using splice-modifying morpholino (MO) resulted in 42%±17% decrease number embryos at 4 days post fertilization. Morphant displayed abnormal development eye,...
Mitochondria are the energy factories of a cell, and depending on metabolic requirements, mitochondrial morphology, quantity, membrane potential in cell change. These changes frequently assessed using commercially available probes. In this study, we tested suitability three probes—namely 5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolo-carbocyanine iodide (JC-1), MitoTracker Red CMX Rox (CMXRos), tetramethylrhodamine methyl ester (TMRM)—for assessing living human mesoangioblasts 3D with...
Detection of mutations in the mitochondrial DNA (mtDNA) is usually limited to common and transfer RNA genes. However, other mtDNA regions can be an important cause oxidative phosphorylation (OXPHOS) disease as well.To investigate whether are preferentially mutated patients with OXPHOS disease.Screening for heteroplasmic was performed by denaturing high-performance liquid chromatography analysis 116 but without mutations.An sequence variant detected 15 patients, 5 which were present ND5 gene....
The TGF-β signaling pathway is a fundamental in the living cell, which plays key role many central cellular processes. complex and sometimes contradicting mechanisms by yields phenotypic effects are not yet completely understood. In this study we investigated compared transcriptional response profile of TGF-β1 stimulation different cell types. For purpose, extensive experiments performed time-course microarray data generated human mouse parenchymal liver cells, mesenchymal stromal cells...