A5028646321- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Metabolism and Genetic Disorders
- Colorectal Cancer Treatments and Studies
- Acute Lymphoblastic Leukemia research
- Cardiomyopathy and Myosin Studies
- Pancreatic and Hepatic Oncology Research
- Genomics and Rare Diseases
- Biochemical and Molecular Research
- RNA modifications and cancer
- Childhood Cancer Survivors' Quality of Life
- HIV/AIDS drug development and treatment
- Renal Transplantation Outcomes and Treatments
- Cytomegalovirus and herpesvirus research
- Neutropenia and Cancer Infections
- Viral Infections and Immunology Research
- Cell Adhesion Molecules Research
- Microtubule and mitosis dynamics
- RNA and protein synthesis mechanisms
- Platelet Disorders and Treatments
- Molecular Biology Techniques and Applications
- Chronic Lymphocytic Leukemia Research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Neurogenetic and Muscular Disorders Research
- Cancer Genomics and Diagnostics
Maastricht University
2009-2025
Maastricht University Medical Centre
2009-2023
Erasmus University Rotterdam
2021
University Medical Center
2019
Amsterdam UMC Location University of Amsterdam
2010
University Medical Center Utrecht
2010
Mitochondrial complex I deficiency is the most common oxidative phosphorylation defect. Mutations have been detected in mitochondrial and nuclear genes, but genetics of many patients remain unresolved new genes are probably involved. In a consanguineous family, presented easy fatigability, exercise intolerance lactic acidosis blood from early childhood. muscle, subsarcolemmal proliferation severe were observed. Exercise activity was improved by supplement riboflavin at high dosage....
In patients with mitochondrial disease a continuously increasing number of DNA (mtDNA) mutations and polymorphisms have been identified. Most pathogenic mtDNA are heteroplasmic, resulting in heteroduplexes after PCR amplification mtDNA. To detect these heteroduplexes, we used the technique denaturing high performance liquid chromatography (DHPLC). The complete genome was amplified 13 fragments 1-2 kb, digested 90-600 bp resolved at their optimal melting temperature. sensitivity DHPLC system...
Mutations in the DNA polymerase-gamma (POLG) gene are a major cause of clinically heterogeneous mitochondrial diseases, associated with mtDNA depletion and multiple deletions.To determine spectrum POLG mutations our Dutch patient cohort, to evaluate pathogenicity novel mutations, establish genotype-phenotype correlations.The authors identified 64 predominantly recessive 37 patients from total 232 patients, consisting 23 different mutations. The substitution p.A467T was most frequently...
Identifying mitochondrial DNA (mtDNA) sequence variants in human diseases is complicated. Many pathological mutations are heteroplasmic, with the mutant allele represented at highly variable percentages. High-resolution melt (HRM or HRMA) profiling was applied to comprehensive assessment of genome and targeted recognized mutations. The assay panel providing coverage utilizes 36 overlapping fragments (301–658 bp) that employ a common PCR protocol. identified heteroplasmic mutation 33 out...
<h3>Background</h3> Leigh syndrome is an early onset, progressive, neurodegenerative disorder with developmental and motor skills regression. Characteristic magnetic resonance imaging abnormalities consist of focal bilateral lesions in the basal ganglia and/or brainstem. The main cause a deficiency oxidative phosphorylation due to mutations mtDNA or nuclear gene. <h3>Methods results</h3> A consanguineous Moroccan family comprise 11 children, three which are affected. Marker analysis revealed...
<h3>Background</h3> Mitochondrial disorders are associated with abnormalities of the oxidative phosphorylation (OXPHOS) system and cause significant morbidity mortality in population. The extensive clinical genetic heterogeneity these due to a broad variety mutations several hundreds candidate genes, encoded by either mitochondrial DNA (mtDNA) or nuclear (nDNA), impedes straightforward diagnosis. A new disease gene is presented here, identified single Kurdish patient born from consanguineous...
Abstract Purpose In 20–30% of the patients, fluoropyrimidines (5-FU) based chemotherapy leads to severe toxicity, which is associated with dihydropyridine dehydrogenase (DPD) deficiency. Therefore, DPYD genotyping became standard practice before treatment fluoropyrimidines. Nevertheless, only 17% patients toxicity have a variant. an urgent need persists investigate other strategies contributing prediction and prevention toxicity. Endogenous DPD substrates are considered as potential...
In a 28-year-old male with mild mitochondrial myopathy manifesting as exercise intolerance and early signs of cardiomyopathy without muscle weakness or ophthalmoplegia, we identified two novel mutations in the SLC25A4 gene: c.707G>C exon 3 (p.(R236P)) c.116_137del 2 (p.(Q39Lfs*14)). Serum lactate levels at rest were elevated (12.7 mM). Both patient's father brother heterozygous carriers mutation asymptomatic. The second causes 22 bp deletion leading to frame shift likely giving rise...
Patients with inflammatory bowel disease (IBD) show large variability in course, and also treatment response. The response has led to many initiatives search of genetic markers optimize avoid severe side effects. This been very successful for thiopurines, one the drugs used induce maintain remission IBD. However, newer options IBD, like biologicals, predictors not yielded any candidate biomarkers clinical utility. In this review, a summary recent advances pharmacogenetics focusing on...
A previously healthy 20-year-old woman was admitted to the department of neurology our hospital after 2 generalized tonic-clonic seizures in preceding weeks. Since first seizure, she had been seeing bright spots. Neurologic examination at admission normal. EEG showed slowed background activity and continuous epileptic left occipital lobe. MRI revealed asymmetric but bilateral areas increased signal intensity cortex, most prominent hemisphere (figure, A). During following weeks, symptoms...
Fluoropyrimidine treatment can be optimized based on dihydropyrimidine dehydrogenase (DPD) activity. DPD dysfunction leads to increased exposure active metabolites, which result in severe or even fatal toxicity.We provide an overview of 8 years diagnostic testing (n = 1194).Within the study period, our test evolved from a single-enzyme measurement using first radiochemical and then nonradiochemical assay by ultra HPLC-MS peripheral blood mononuclear cells with uracil, combined enzymatic...
6-mercaptopurine (6-MP) is the mainstay in pediatric acute lymphoblastic leukemia (ALL) maintenance treatment. Variants genes coding for thiopurine S-methyl transferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) are known to influence 6-MP metabolism. We determined TPMT ITPA genotype enzyme activity mean doses during treatment 40 children treated ALL according Dutch Childhood Oncology Group (DCOG)-ALL11 protocol Radboudumc Amalia Children’s Hospital, Nijmegen, The Netherlands....