A5013074656- Alzheimer's disease research and treatments
- Drug Transport and Resistance Mechanisms
- RNA and protein synthesis mechanisms
- Cholesterol and Lipid Metabolism
- Trace Elements in Health
- RNA Research and Splicing
- MicroRNA in disease regulation
- Genomics and Phylogenetic Studies
- Cellular transport and secretion
- Cardiac Valve Diseases and Treatments
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Intracerebral and Subarachnoid Hemorrhage Research
- Infective Endocarditis Diagnosis and Management
- Mitochondrial Function and Pathology
- Cell Adhesion Molecules Research
- Cardiac Imaging and Diagnostics
- Lipoproteins and Cardiovascular Health
- Cardiac, Anesthesia and Surgical Outcomes
- Lung Cancer Treatments and Mutations
- Cerebrovascular and genetic disorders
- Cholinesterase and Neurodegenerative Diseases
- Retinal Development and Disorders
- Genetic Neurodegenerative Diseases
- Machine Learning in Bioinformatics
- Genomics and Rare Diseases
University of Antwerp
2018-2024
VIB-UAntwerp Center for Molecular Neurology
2018-2024
Bunge & Born Foundation
2020-2021
Technological limitations have hindered the large-scale genetic investigation of tandem repeats in disease. We show that long-read sequencing with a single Oxford Nanopore Technologies PromethION flow cell per individual achieves 30× human genome coverage and enables accurate assessment including 10,000-bp Alzheimer's disease-associated ABCA7 VNTR. The Guppy "flip-flop" base caller tandem-genotypes repeat are efficient for assessment, but calling alignment challenges persist. present...
Truncating genetic variants of SORL1 , encoding the endosome recycling receptor SORLA, have been accepted as causal Alzheimer’s disease (AD). However, most observed in are missense variants, for which it is complicated to determine pathogenicity level because carriers come from pedigrees too small be informative penetrance estimations. Here, we describe three unrelated families coding variant rs772677709, that leads a p.Y1816C substitution, segregates with disease. Further, investigate...
The adenosine triphosphate-binding cassette subfamily A member 7 gene (ABCA7) is associated with Alzheimer's disease (AD) in large genome-wide association studies. Targeted sequencing of ABCA7 suggests a role for rare premature termination codon (PTC) mutations AD, haploinsufficiency through nonsense-mediated mRNA decay as plausible pathogenic mechanism. Since other classes variants are poorly understood, we investigated the contribution and pathogenicity missense, indel splice Belgian AD...
The ATP-Binding Cassette Subfamily A Member 7 gene (ABCA7) was identified as a risk for Alzheimer's disease (AD) in genome-wide association studies of large cohorts late-onset AD (LOAD) patients. Extended resequencing the ABCA7 coding regions mutations that lead to premature termination codons (PTC) and loss function ABCA7. PTC were enriched LOAD patients frequently present with early-onset (EOAD). We aimed at assessing contribution Belgian population by screening region cohort 1376...
The aim of this study was to determine if computed tomography (CT) psoas muscular attenuation measurements may predict all-cause mortality in patients undergoing TAVI.Ninety-four consecutive TAVI were analysed. CT axial slice at the level fourth lumbar vertebra selected. muscle areas manually contoured. circumferential surface area (CSA) both muscles determined by selecting voxels with values, ranging from 0 100 Hounsfield Units (HU). mean coefficient (Psoas HU) measured. subdivided into a...
ABSTRACT Truncating genetic variants of SORL1 , encoding the endosome recycling receptor SORLA, have been accepted as causal Alzheimer’s disease (AD). However, most observed in are missense variants, for which it is complicated to determine pathogenicity level because carriers come from pedigrees too small be informative penetrance estimations. Here, we describe three unrelated families coding variant rs772677709, that leads a p.Y1816C substitution, segregates with disease. Further,...
Abstract Tandem repeats (TRs) can cause disease through their length, sequence motif interruptions, and nucleotide modifications. For many TRs, however, these features are very difficult - if not impossible to assess, requiring low-throughput labor-intensive assays. One example is a VNTR in ABCA7 for which we recently discovered that expanded alleles strongly increase risk of Alzheimer’s disease. Here, investigated the potential long-read whole genome sequencing surmount challenges, using...
Quantifiable biomarkers may be useful for a better risk and frailty assessment of patients referred transcatheter aortic valve implantation (TAVI).To determine if adiponectin serum concentration predicts all-cause mortality in undergoing TAVI.77 consecutive patients, TAVI, were analyzed. The CT axial slices at the level fourth lumbar vertebra used to measure psoas muscle area, its low-density fraction (LDM (%)). To assess operative risk, STS (Society Thoracic Surgeons Predicted Risk...
Sunday, April 26April 14, 2020Free AccessIn a Large Belgian AD Cohort Loss of ABCA7 Mutations Are Associated with Alzheimer’s Disease and Cerebral Amyloid Angiopathy. (1779)Elisabeth Hens, Liene Bossaerts, Tobi Van den Bossche, Sebastiaan Engelborghs, Karin Peeters, Marleen Broeck, Yannick Vermeiren, … Show All , Annelies Laureys, Naomi De Roeck, Bernard Hanseeuw, Anne Sieben, Rik Vandenberghe, Jean-Jacques Martin, Peter Deyn, Patrick Cras, Christine Broeckhoven FewerAuthors Info &...
Abstract Background Genetic screening of our Belgian Alzheimer’s Disease (AD) cohort (n = 1478) observed in 69 patients, 15 different premature termination codon (PTC) mutations the gene coding ATP‐Binding Cassette Subfamily A Member 7 (ABCA7) leading to loss ABCA7 protein. We aimed delineate clinicopathological AD phenotype mutation carriers. The was initially identified as a risk genome wide association studies large patient cohorts. Methods Reviewing available demographic and 44) clinical...
Abstract Background ABCA7 was initially associated with Alzheimer’s disease (AD) in genome‐wide association studies. Recent genetic studies suggest a role for rare premature termination codon (PTC) mutations . While we observed loss of protein PTC mutations, there high variability between due to transcript rescue. Apart from are missense unknown effect on protein. Segregation patterns and pathogenicity still poorly understood. We aimed at investigating the contribution Belgian AD control...
Abstract Background The ATP‐Binding Cassette Subfamily A member 7 ( ABCA7 ) gene is one of most alluring risk genes for Alzheimer’s disease (AD). Of special interest are alternative splice events that a) able to rescue the effect premature termination codon (PTC) mutations, possibly explaining wide range in phenotype and onset age PTC mutation carriers, b) associated with an elongated intronic variable number tandem repeat (VNTR). However, our knowledge limited. Here, we analyze transcript...
Abstract Background ABCA7 is a major risk gene for Alzheimer’s disease (AD) and rare premature termination codon (PTC) missense mutations are enriched in AD patients. In preliminary studies we obtained that PTC mutation carriers present with classic phenotype, but severe levels of cerebral amyloid angiopathy (CAA) were also found (table 1, figures 1‐2). We aim to delineate the clinicopathological phenotype Belgian CAA Methods Genetic screening cohort (n = 83), genotype‐phenotype comparison...
Initially, ABCA7 was associated with Alzheimer's disease (AD) in large genome-wide association studies. Targeted resequencing of suggested a role for rare premature termination codon (PTC) mutations. We observed loss PTC carriers, although high variability due to differences transcript rescue. Additionally, missense mutations are present unknown effect on the protein. aimed investigate contribution (MAF≤1%) or compound heterozygous Belgian AD patient and control cohorts, as well subcellular...
To delineate the clinicopathological Alzheimer's disease (AD) phenotype of ABCA7 missense mutation carriers, and to compare genotype–phenotype data with AD patients carrying an premature termination codon (PTC) variant. was associated risk for in GWAS, rare PTC variants are enriched patients.