Elke de Boer
A5075023136- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Genetics and Neurodevelopmental Disorders
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- Congenital heart defects research
- RNA modifications and cancer
- Animal Genetics and Reproduction
- RNA Research and Splicing
- Genomics and Phylogenetic Studies
- Immunodeficiency and Autoimmune Disorders
- Health, Environment, Cognitive Aging
- Genetic Syndromes and Imprinting
- Craniofacial Disorders and Treatments
- Solid-state spectroscopy and crystallography
- Optical properties and cooling technologies in crystalline materials
- Genetic and phenotypic traits in livestock
- CRISPR and Genetic Engineering
- Congenital Ear and Nasal Anomalies
- Blood groups and transfusion
- Molecular Biology Techniques and Applications
- Congenital limb and hand anomalies
- Prenatal Screening and Diagnostics
- Lysosomal Storage Disorders Research
Radboud University Nijmegen
1995-2024
Radboud University Medical Center
2018-2024
University Medical Center
2018-2023
Erasmus MC
2023
Radboud Institute for Molecular Life Sciences
2023
University of Edinburgh
1988
University of Wisconsin–Madison
1988
Abstract Hereditary congenital facial paresis type 1 (HCFP1) is an autosomal dominant disorder of absent or limited movement that maps to chromosome 3q21-q22 and hypothesized result from branchial motor neuron (FBMN) maldevelopment. In the present study, we report HCFP1 results heterozygous duplications within a neuron-specific GATA2 regulatory region includes two enhancers one silencer, noncoding single-nucleotide variants (SNVs) silencer. Some SNVs impair binding NR2F1 silencer in vitro...
Summary De novo mutations (DNMs) in protein-coding genes are a well-established cause of developmental disorders (DD). However, known DD-associated only account for minority the observed excess such DNMs. To identify novel genes, we integrated healthcare and research exome sequences on 31,058 DD parent-offspring trios, developed simulation-based statistical test to gene-specific enrichments We identified 285 significantly including 28 not previously robustly associated with DDs. Despite...
Although haploinsufficiency of ANKRD11 is among the most common genetic causes neurodevelopmental disorders, role rare missense variation remains unclear. We characterized clinical, molecular, and functional spectra variants.
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 short lengths of short-read sequencing reads challenge the analysis paralogous genomic regions in exome and genome data. Most genetic variants within these homologous therefore remain unidentified standard analyses. Here, we present a method (Chameleolyser) that accurately identifies single nucleotide small insertions/deletions (SNVs/Indels), copy number ectopic gene conversion events duplicated using whole-exome Application to cohort 41,755 samples yields 20,432 rare homozygous...
Abstract Dubowitz syndrome (DubS) is considered a recognizable characterized by distinctive facial appearance and deficits in growth development. There have been over 200 individuals reported with or “Dubowitz‐like” condition, although no single gene has implicated as responsible for its cause. We performed exome (ES) genome sequencing (GS) 31 clinically diagnosed DubS. After genome‐wide sequencing, rare variant filtering computational Mendelian genomic analyses, presumptive molecular...
Summary De novo mutations (DNMs) in protein-coding genes are a well-established cause of developmental disorders (DD). However, known DD-associated only account for minority the observed excess such DNMs. To identify novel genes, we integrated healthcare and research exome sequences on 31,058 DD parent-offspring trios, developed simulation-based statistical test to gene-specific enrichments We identified 299 significantly including 49 not previously robustly associated with DDs. Despite...
The genetic etiology of intellectual disability remains elusive in almost half all affected individuals. Within the Solve-RD consortium, systematic re-analysis whole exome sequencing (WES) data from unresolved cases with (syndromic) (n = 1,472 probands) was performed. This included variant calling mitochondrial DNA (mtDNA) variants, although mtDNA is not specifically targeted WES. We identified a functionally relevant MT-TL1 (NC_012920.1:m.3291T > C; NC_012920.1:n.62T C), at heteroplasmy...
In biomedical research, particularly for rare diseases (RDs), there is a critical need model organisms to unravel the mechanistic basis of diseases, perform biomarker studies and develop potential therapeutic interventions. Within Solve-RD, an EU-funded research project with aim solving large numbers previously unsolved RDs, European Rare Disease Models & Mechanisms Network (RDMM-Europe) has been established.
The collection of the Narrenturm in Vienna houses and maintains more than 50,000 objects including approximately 1200 teratological specimens; making it one biggest collections specimens from human origin Europe. existence this magnificent collection-representing an important resource for dysmorphology research, mostly awaiting contemporary diagnoses-is not widely known scientific community. Here, we show that harbors a wealth with (exceptionally) rare congenital anomalies. These museums can...
Abstract While both molecular and phenotypic data are essential when interpreting genetic variants, prediction scores (CADD, PolyPhen, SIFT) have focused on details to evaluate pathogenicity — omitting features. To unlock the full potential of data, we developed PhenoScore: an open source, artificial intelligence-based phenomics framework. PhenoScore combines facial recognition technology with Human Phenotype Ontology (HPO) analysis quantify similarity at level individual patients as well...
Split-hand/foot malformation (SHFM) is a congenital limb defect most typically presenting with median clefts in hands and/or feet, that can occur syndromic context as well isolated form. SHFM caused by failure to maintain normal apical ectodermal ridge function during development. Although several genes and contiguous gene syndromes are implicated the monogenic etiology of SHFM, disorder remains genetically unexplained for many families associated genetic loci. We describe family X-linked...
Abstract We report the diagnostic results of a comprehensive copy number variant (CNV) reanalysis 9,171 exome sequencing (ES) datasets from 5,757 families, including 6,143 individuals affected by rare disease (RD). The data analysed was extremely heterogeneous, having been generated using 28 different enrichment kits, and sequenced on multiple short-read platforms, 42 research groups across Europe partnering in Solve-RD project. Each these had previously undertaken their own analysis ES but...