A5016607178- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Retinal Development and Disorders
- Genetic factors in colorectal cancer
- Genomics and Phylogenetic Studies
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Retinal Diseases and Treatments
- Autism Spectrum Disorder Research
- Cardiac, Anesthesia and Surgical Outcomes
- Trace Elements in Health
- Cardiac Arrest and Resuscitation
- Cardiac and Coronary Surgery Techniques
- Genetics and Neurodevelopmental Disorders
- Protein Tyrosine Phosphatases
- RNA regulation and disease
- Medical Imaging and Pathology Studies
- Ophthalmology and Visual Impairment Studies
- Mitochondrial Function and Pathology
Radboud University Nijmegen
2021-2025
Radboud University Medical Center
2021-2025
St. Antonius Ziekenhuis
2024
Genome sequencing (GS) can identify novel diagnoses for patients who remain undiagnosed after routine diagnostic procedures. We tested whether GS is a better first-tier genetic test than current standard of care (SOC) by assessing the technical and clinical validity with neurodevelopmental disorders (NDD). performed both exome in 150 consecutive NDD patient-parent trios. The primary outcome was yield, calculated from disease-causing variants affecting exonic sequence known genes. (30%, n =...
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...
Abstract Solve-RD is a pan-European rare disease (RD) research program that aims to identify disease-causing genetic variants in previously undiagnosed RD families. We utilised 10-fold coverage HiFi long-read sequencing (LRS) for detecting causative structural (SVs), single nucleotide (SNVs), insertion-deletions (InDels), and short tandem repeat (STR) expansions extensively studied families without clear molecular diagnoses. Our cohort includes 293 individuals from 114 genetically selected...
Solve-RD is a pan-European rare disease (RD) research program that aims to identify disease-causing genetic variants in previously undiagnosed RD families. We utilized 10-fold coverage HiFi long-read sequencing (LRS) for detecting causative structural (SVs), single-nucleotide (SNVs), insertion-deletions (indels), and short tandem repeat (STR) expansions studied families without clear molecular diagnosis. Our cohort includes 293 individuals from 114 genetically selected by European Reference...
Mobile element insertions (MEIs) are a known cause of genetic disease but have been underexplored due to technical limitations testing methods. Various bioinformatic tools developed identify MEIs in Next Generation Sequencing data. However, most specifically for genome sequencing (GS) data rather than exome (ES) data, which remains more widely used routine diagnostic testing. In this study, we benchmarked six MEI detection (ERVcaller, MELT, Mobster, SCRAMble, TEMP2 and xTea) on ES GS from...
The lack of molecular diagnoses in rare genetic diseases can be explained by limitations current standard genomic technologies. Upcoming long-read techniques have complementary strengths to overcome these limitations, with a particular strength identifying structural variants. By using optical genome mapping and sequencing, we aimed identify the pathogenic variant large family X-linked choroideremia. In this family, aberrant splicing exon 12 choroideremia gene CHM was detected 2003, but...
Abstract Pathogenic variants in the OPN1LW/OPN1MW gene cluster are causal for a range of mild to severe visual impairments with color deficiencies. The widely utilized short-read next-generation sequencing (NGS) is inappropriate analysis and many patients pathogenic stay underdiagnosed. A diagnostic genetic assay was developed cluster, consisting copy number via multiplex ligation-dependent probe amplification sequence long-read circular consensus sequencing. Performance determined on 50...
Clinical short-read exome and genome sequencing approaches have positively impacted diagnostic testing for rare diseases. Yet, technical limitations associated with short reads challenge their use detection of disease-associated variation in complex regions the genome. Long-read (LRS) technologies may overcome these challenges, potentially qualifying as a first-tier test all To this hypothesis, we performed LRS (30x HiFi genomes) 100 samples 145 known clinically relevant germline variants...
Objective During cardiopulmonary bypass (CPB), gaseous microemboli (GME) that originate from the extracorporeal circuit are released into arterial blood stream of patient. Gaseous may contribute to adverse outcome after cardiac surgery with CPB. Possibly, air be collected in right atrium during induction anesthesia and CPB start. The aim this study was assess if GME load entering venous line could reduced by training personal avoiding introduction administration intravenous medication....
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 GS (NovaSeq ™ 6000; 37x mean coverage) on 1,000 cases with 1,271 known clinically...