A5057619639- Prenatal Screening and Diagnostics
- Genomic variations and chromosomal abnormalities
- Hedgehog Signaling Pathway Studies
- Cancer Genomics and Diagnostics
- Cardiac electrophysiology and arrhythmias
- Genomics and Rare Diseases
- Assisted Reproductive Technology and Twin Pregnancy
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Birth, Development, and Health
- BRCA gene mutations in cancer
- Glutathione Transferases and Polymorphisms
- Adipose Tissue and Metabolism
- Cystic Fibrosis Research Advances
- Genetic Syndromes and Imprinting
- Epigenetics and DNA Methylation
- Cancer and Skin Lesions
- Genetic and rare skin diseases.
- Fetal and Pediatric Neurological Disorders
- Reproductive Health and Technologies
- Soft tissue tumor case studies
- Renal and related cancers
- Neurofibromatosis and Schwannoma Cases
- Neurogenetic and Muscular Disorders Research
- Mitochondrial Function and Pathology
Maastricht University
2015-2024
Maastricht University Medical Centre
2013-2024
University Medical Center
2013-2023
Hendrix Genetics (Netherlands)
2010
Johnson & Johnson (United States)
2002
Zero to Three
2000
Janssen (Belgium)
2000
Our aim was to compare the accuracy of family- or disease-specific targeted haplotyping and direct mutation-detection strategies with genome-wide mapping parental origin each chromosome, karyomapping, by single-nucleotide polymorphism genotyping parents, a close relative known disease status, embryo cell(s) used for preimplantation genetic diagnosis single-gene defects in single cell small numbers cells biopsied from human embryos following vitro fertilization.Genomic DNA whole-genome...
Kabuki Syndrome (KS) is a rare syndrome characterized by intellectual disability and multiple congenital abnormalities, in particular distinct dysmorphic facial appearance. KS caused mutations the MLL2 gene, encoding an H3K4 histone methyl transferase which acts as epigenetic transcriptional activator during growth development. Direct sequencing of all 54 exons gene 45 clinically well-defined patients identified 34 (75.6%) different mutations. One mutation has been described previously,...
The purpose of this study was to explore the diagnostic yield and clinical utility trio-based rapid whole exome sequencing (rWES) in pregnancies fetuses with a wide range congenital anomalies detected by ultrasound imaging.In observational study, we analyzed first 54 cases referred our laboratory for prenatal rWES support decision making, after sonographic detection fetal anomalies. most common identified were skeletal dysplasia (n = 20), multiple major 17) intracerebral structural 7).A...
Pregnancy loss is often caused by chromosomal abnormalities of the conceptus. The prevalence these and allocation (ab)normal cells in embryonic placental lineages during intrauterine development remain elusive. In this study, we analyzed 1,745 spontaneous pregnancy losses found that roughly half (50.4%) products conception (POCs) were karyotypically abnormal, with maternal paternal age independently contributing to increased genomic aberration rate. We applied genome haplarithmisis a subset...
Abstract Background To diagnose the full spectrum of hereditary and congenital diseases, genetic laboratories use many different workflows, ranging from karyotyping to exome sequencing. A single generic high-throughput workflow would greatly increase efficiency. We assessed whether genome sequencing (GS) can replace these existing workflows aimed at germline diagnosis for rare disease. Methods performed short-read GS (NovaSeq™6000; 150 bp paired-end reads, 37 × mean coverage) on 1000 cases...
We determined the genetic contribution of 18 anthropometric and metabolic risk factors type 2 diabetes using a young healthy twin population.Traits were measured in 240 monozygotic (MZ) 138 dizygotic (DZ) pairs aged to 34 years. Twins recruited from Belgian population-based East Flanders Prospective Twin Survey, which is characterised by its accurate zygosity determination extensive collection perinatal placental data, including information on chorionicity. Heritability was estimated...
<h3>Background:</h3> Holoprosencephaly (HPE) is the most common structural malformation of human forebrain. There are several important HPE mutational target genes, including transcription factor <i>SIX3</i>, which encodes an early regulator Shh, Wnt, Bmp and Nodal signalling expressed in developing forebrain eyes all vertebrates. <h3>Objective:</h3> To characterise genetic clinical findings patients with <i>SIX3</i> mutations. <h3>Methods:</h3> Patients their family members were tested for...
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...
Abstract STUDY QUESTION Can reduced representation genome sequencing offer an alternative to single nucleotide polymorphism (SNP) arrays as a generic and genome-wide approach for comprehensive preimplantation genetic testing monogenic disorders (PGT-M), aneuploidy (PGT-A) structural rearrangements (PGT-SR) in human embryo biopsy samples? SUMMARY ANSWER Reduced sequencing, with OnePGT, offers generic, next-generation sequencing-based automated haplotyping copy-number assessment, both combined...
High-throughput sequencing technologies have increasingly led to discovery of disease-causing genetic variants, primarily in postnatal multi-cell DNA samples. However, applying these preimplantation testing (PGT) nuclear or mitochondrial from single few-cells biopsied vitro fertilised (IVF) embryos is challenging. PGT aims select IVF without abnormalities. Although genotyping-by-sequencing (GBS)-based haplotyping methods enabled for monogenic disorders (PGT-M), structural rearrangements...
Mutations within either the SHH gene or its related pathway components are most common, and best understood, pathogenetic changes observed in holoprosencephaly patients; this fact is consistent with essential functions of during forebrain development patterning. Here we summarize nature types deleterious sequence alterations among over one hundred distinct mutations (64 novel mutations) compare these to a dozen disease-related Hedgehog family members IHH DHH. This combined structural...
A recent clinical trial of controlled-release carbidopa/levodopa preparation afforded us the opportunity to examine effects chronically increasing circulating 3-O-methyldopa (OMD) levels on response levodopa. In patients taking standard Sinemet, both mean plasma OMD and area under concentration- versus-time curve (AUC) obtained during 8-hour periods blood sampling correlated highly with total daily intake formulation, levodopa was doubled. This, in turn, led a doubling level its AUC, whereas...
Therapeutic drug monitoring of active metabolites thiopurines, azathioprine and 6-mercaptopurine, is relatively new. The proposed therapeutic threshold level the 6-thioguanine nucleotides (6-TGN) ≥235 pmol/8×10(8) erythrocytes. aim this prospective cross-sectional study was to compare 6-TGN levels in adult thiopurine tolerant IBD patients with an exacerbation those remission, determine cut-off level.Hundred were included. Outcome measures metabolite levels, calculated level, CDAI/CAI scores,...
Consanguineous couples are at increased risk of being heterozygous for the same autosomal recessive (AR) disorder(s), with a 25% affected offspring as consequence. Until recently, comprehensive preconception carrier testing (PCT) AR disorders was unavailable in routine diagnostics. Here we developed and implemented such test clinical care.We performed exome sequencing (ES) 100 consanguineous couples. For each couple, rare variants that could give rise to biallelic were selected. These...
The congenital long QT syndrome is a cardiac disease characterized by an increased susceptibility to ventricular arrhythmias. clinical hallmark prolongation of the interval, which reflects delay in repolarization caused mutations ion channel genes. Mutations HERG (humane <i>ther-à-go-go</i>-relatedgene <i>KCNH2</i> can cause reduction I<sub>Kr</sub>, one currents responsible for repolarization. We describe identification and characterization novel missense mutation T65P PAS (Per-Arnt-Sim)...
Cytochrome P450 3A subfamily members (CYP3A) are the most abundant liver cytochrome forms, responsible for biotransformation of over 50% all drugs. The expression and activity isoforms CYP3A4 CYP3A5 show wide inter-individual variation, influencing both drug response disease susceptibility. molecular basis this variation has never been defined. In study, we used midazolam to characterize phenotype in a panel samples. A clear bimodality metabolism was observed. Analysis 5' flanking region...
We have hypothesized that consumption of fruit and vegetables may be associated with reduced risk bladder cancer this interact cigarette smoking metabolic genetic polymorphisms. A population-based case-control study was performed in the Belgian province Limburg among 200 cases 385 controls. Logistic regression to calculate odds ratios (ORs) for occurrence corresponding 95% confidence intervals (95% CI). Effect modification by investigated. also evaluated interaction between intake GSTM1,...
Mutations of the ZIC2 transcription factor gene are among most common heterozygous variations detected in holoprosencephaly (HPE) patients, a patient group who lack critical midline forebrain specification due to defective embryonic signaling during development. Recent studies indicate that complete deficiency related murine Zic2 can also be contributing variable deficiencies, presenting mid-gastrulation, could explain similar anomalies this model system. Here we collect and summarize all...
The aim of this study was to determine whether BRCA1/2 mutation carriers produce fewer mature oocytes after ovarian stimulation for in vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD), comparison a PGD control group.A retrospective, international, multicenter cohort performed on data first cycles between January 2006 and September 2015. Data were extracted from medical files. one center three affiliated IVF centers the Netherlands Belgium. Exposed couples underwent...
Does germline selection (besides random genetic drift) play a role during the transmission of heteroplasmic pathogenic mitochondrial DNA (mtDNA) mutations in humans? We conclude that inheritance mtDNA is mutation-specific and governed by combination drift negative and/or positive selection. inherits maternally through bottleneck, but underlying mechanisms are largely unknown. Although recognized as an important mechanism, thought to well. determined mutation loads 160 available oocytes,...