A5059939296- Prenatal Screening and Diagnostics
- Genomic variations and chromosomal abnormalities
- Genomics and Rare Diseases
- Fetal and Pediatric Neurological Disorders
- Cancer Genomics and Diagnostics
- Congenital heart defects research
- Advanced biosensing and bioanalysis techniques
- Genetic Syndromes and Imprinting
- Chromosomal and Genetic Variations
- Biomedical Text Mining and Ontologies
- Genomics and Phylogenetic Studies
- Cardiomyopathy and Myosin Studies
- RNA modifications and cancer
- Assisted Reproductive Technology and Twin Pregnancy
- Metabolism and Genetic Disorders
- Congenital Ear and Nasal Anomalies
- Congenital Heart Disease Studies
- Genetics and Neurodevelopmental Disorders
- Reproductive Biology and Fertility
- Congenital Anomalies and Fetal Surgery
- CRISPR and Genetic Engineering
- Molecular Biology Techniques and Applications
- Genetic Neurodegenerative Diseases
- Acute Myeloid Leukemia Research
- RNA and protein synthesis mechanisms
University Medical Center Groningen
2016-2025
University of Groningen
2016-2025
John Wiley & Sons (United Kingdom)
2020
Hudson Institute
2020
University of Amsterdam
2007-2019
Amsterdam University Medical Centers
2019
Genetikum
2017
Early Intervention Foundation
1998-2016
Hendrix Genetics (Netherlands)
2011
Leiden University
2009
Pregnancy rates in women of advanced maternal age undergoing vitro fertilization (IVF) are disappointingly low. It has been suggested that the use preimplantation genetic screening cleavage-stage embryos for aneuploidies may improve effectiveness IVF these women.We conducted a multicenter, randomized, double-blind, controlled trial comparing three cycles with and without 35 through 41 years age. The primary outcome measure was ongoing pregnancy at 12 weeks gestation. secondary measures were...
The Netherlands launched a nationwide implementation study on non-invasive prenatal testing (NIPT) as first-tier test offered to all pregnant women. This started April 1, 2017 the TRIDENT-2 study, licensed by Dutch Ministry of Health. In first year, NIPT was performed in 73,239 pregnancies (42% pregnancies), 7,239 (4%) chose first-trimester combined testing, and 54% did not participate. number trisomies 21 (239, 0.33%), 18 (49, 0.07%), 13 (55, 0.08%) found this is comparable earlier studies,...
Mutation detection through exome sequencing allows simultaneous analysis of all coding sequences genes. However, it cannot yet replace Sanger (SS) in diagnostics because incomplete representation and coverage exons leading to missing clinically relevant mutations. Targeted next-generation (NGS), which a selected fraction genes is sequenced, may circumvent these shortcomings. We aimed determine whether the sensitivity specificity targeted NGS equal those SS. constructed enrichment kit that...
Childhood-onset pulmonary arterial hypertension (PAH) is rare and differs from adult-onset disease in clinical presentation, with often unexplained mental retardation dysmorphic features (MR/DF). Mutations the major PAH gene, BMPR2, were reported to cause only 10-16% of childhood-onset patients. We aimed identify more genes associated PAH.We studied 20 consecutive cases idiopathic or heritable PAH. In patients accompanying MR/DF (n=6) array-comparative genomic hybridisation analysis was...
BACKGROUND: Rapid diagnostic whole-genome sequencing has been explored in critically ill newborns, hoping to improve their clinical care and replace time-consuming and/or invasive testing. A previous retrospective study a research setting showed promising results with diagnoses 57%, but patients were highly selected for known likely Mendelian disorders. The aim of our prospective was assess the speed yield rapid targeted genomic diagnostics application. METHODS: We included 23 children...
Abstract The diagnostic yield of exome and genome sequencing remains low (8–70%), due to incomplete knowledge on the genes that cause disease. To improve this, we use RNA-seq data from 31,499 samples predict which specific disease phenotypes, develop GeneNetwork Assisted Diagnostic Optimization (GADO). We show this unbiased method, does not rely upon individual genes, is effective in both identifying previously unknown gene associations, flagging have been incorrectly implicated GADO can be...
We have developed a tool for detecting single exon copy-number variations (CNVs) in targeted next-generation sequencing data: CoNVaDING (Copy Number Variation Detection In Next-generation Gene panels). includes stringent quality control (QC) metric, that excludes or flags low-quality exons. Since this QC shows exactly which exons can be reliably analyzed and are need of an alternative analysis method, is not only useful CNV detection research setting, but also clinical diagnostics. During...
In this study, we compare next-generation sequencing (NGS) approaches (targeted panel (tNGS), whole exome (WES), and genome (WGS)) for application in newborn screening (NBS). DNA was extracted from dried blood spots (DBS) 50 patients with genetically confirmed inherited metabolic disorders (IMDs) control samples. One hundred IMD-related genes were analyzed. Two data-filtering strategies applied: one to detect only (likely) pathogenic ((L)P) variants, (L)P variants combination of unknown...
Clinical and genetic heterogeneity in monogenetic disorders represents a major diagnostic challenge. Although the presence of particular clinical features may aid identifying specific cause some cases, majority patients remain undiagnosed. Here, we investigated utility whole-exome sequencing as approach for establishing molecular diagnosis highly heterogeneous group with varied intellectual disability microcephaly.Whole-exome was performed 38 patients, including three sib-pairs, addition to...
Genome-wide arrays are rapidly replacing conventional karyotyping in postnatal cytogenetic diagnostics and there is a growing request for the prenatal setting. Several studies have documented 1–3% additional abnormal findings diagnosis with compared to karyotyping. A recent meta-analysis demonstrated that 5.2% extra diagnoses can be expected fetuses ultrasound abnormalities. However, no consensus exists as whether use of genome-wide should restricted pregnancies abnormalities, performed all...
We present Gene-Aware Variant INterpretation (GAVIN), a new method that accurately classifies variants for clinical diagnostic purposes. Classifications are based on gene-specific calibrations of allele frequencies from the ExAC database, likely variant impact using SnpEff, and estimated deleteriousness CADD scores >3000 genes. In benchmark 18 gene sets, we achieve sensitivity 91.4% specificity 76.9%. This accuracy is unmatched by 12 other tools. provide GAVIN as an online MOLGENIS service...
Inherited neurological disorders, such as spinocerebellar ataxia (SCA) and fragile X (FraX), are frequently caused by short tandem repeat (STR) expansions. The detection assessment of STRs is important for diagnostics prognosis. We tested the abilities nanopore long-read sequencing (LRS) using a custom panel including nine most common SCA-related genes FraX created raw data to report workflow. Using known STR lengths 23 loci in 12 patients, pipeline was validated detect lengths. In addition,...
The introduction of genome-wide arrays in postnatal and prenatal diagnosis raises challenging ethical issues. Here, we explore questions with regard to the ethics consent. One important issue is whether informed consent for array-based testing fact feasible, given wide range possible outcomes related options. proposed alternative "generic consent" will have be studied practice. From an point view, question would still sufficiently "informed" a generic approach. Another that has not yet been...
22q11.2 deletion syndrome is one of the most common microdeletion syndromes. Most patients have a resulting from recombination low copy repeat blocks LCR22‐A and LCR22‐D. Loss TBX1 gene considered important cause phenotype. A limited number with smaller, overlapping deletions distal to TBX 1 locus been described in literature. In these patients, CRKL deleted. Haploinsufficiency this has also implicated pathogenesis syndrome. To distinguish (comprising LCR22‐B LCR22‐D region) more (located...
Exome sequencing is now mainstream in clinical practice. However, identification of pathogenic Mendelian variants remains time-consuming, part, because the limited accuracy current computational prediction methods requires manual classification by experts. Here we introduce CAPICE, a new machine-learning-based method for prioritizing variants, including SNVs and short InDels. CAPICE outperforms best general (CADD, GAVIN) consequence-type-specific (REVEL, ClinPred) methods, both rare...
Abstract Objective Conventional genetic tests (quantitative fluorescent‐PCR [QF‐PCR] and single nucleotide polymorphism‐array) only diagnose ~40% of fetuses showing ultrasound abnormalities. Rapid exome sequencing (rES) may improve this diagnostic yield, but includes challenges such as uncertainties in fetal phenotyping, variant interpretation, incidental unsolicited findings, rapid turnaround times. In study, we implemented rES prenatal care to increase yield. Methods We prospectively...