A5062559130- Connective tissue disorders research
- Heterotopic Ossification and Related Conditions
- Bone and Dental Protein Studies
- Medical Imaging and Pathology Studies
- Aortic aneurysm repair treatments
- Parathyroid Disorders and Treatments
- Aortic Disease and Treatment Approaches
- Bone health and treatments
- Protease and Inhibitor Mechanisms
- Genetic Syndromes and Imprinting
- Genetic and Kidney Cyst Diseases
- Cystic Fibrosis Research Advances
- Infectious Aortic and Vascular Conditions
- Bone health and osteoporosis research
- Neonatal Respiratory Health Research
- Vitamin K Research Studies
- Bone fractures and treatments
- Esophageal and GI Pathology
- Mesenchymal stem cell research
- Bone Metabolism and Diseases
- dental development and anomalies
- Genomics and Rare Diseases
- TGF-β signaling in diseases
- Macrophage Migration Inhibitory Factor
- Tracheal and airway disorders
Vrije Universiteit Amsterdam
2011-2025
Amsterdam University Medical Centers
2019-2025
Amsterdam UMC Location Vrije Universiteit Amsterdam
2012-2024
GGD Amsterdam
2024
University of Amsterdam
2022-2024
Institute for Atherosclerosis Research
2017
Diponegoro University
2017
Leiden University Medical Center
2015
Radboud University Nijmegen
2015
Amsterdam UMC Location University of Amsterdam
2015
Defects in motile cilia and sperm flagella cause primary ciliary dyskinesia (PCD), characterized by chronic airway disease, infertility, left-right laterality disturbances, usually as a result of loss the outer dynein arms (ODAs) that power cilia/flagella beating. Here, we identify loss-of-function mutations <i>CCDC114</i> causing PCD with malformations involving complex heart defects. CCDC114 is homologous to DCC2, an ODA microtubule-docking component biflagellate alga <i>Chlamydomonas.</i>...
Plastin 3 (PLS3), a protein involved in the formation of filamentous actin (F-actin) bundles, appears to be important human bone health, on basis pathogenic variants PLS3 five families with X-linked osteoporosis and osteoporotic fractures that we report here. The bone-regulatory properties were supported by vivo analyses zebrafish. Furthermore, an additional (described less detail) referred for diagnosis or ruling out osteogenesis imperfecta type I, rare variant (rs140121121) was found. This...
It has been shown that losartan reduces aortic dilatation in patients with Marfan syndrome. However, treatment response is highly variable. This study investigates effectiveness genetically classified subgroups.In this predefined substudy of COMPARE, were randomized to daily receive 100 mg or no losartan. Aortic root dimensions measured by MRI at baseline and after 3 years. FBN1 mutations based on fibrillin-1 protein effect into (1) haploinsufficiency, decreased amount normal fibrillin-1,...
Defects in motile cilia and sperm flagella cause primary ciliary dyskinesia (PCD), characterized by chronic airway disease, infertility, left-right body axis disturbance. Here we report maternally inherited de novo mutations PIH1D3 four men affected with PCD. is located on the X chromosome involved preassembly of both outer (ODA) inner (IDA) dynein arms flagella. Loss-of-function lead to absent ODAs reduced IDAs, causing flagellar immotility. Further, interacts co-precipitates cytoplasmic...
Water is known to play an important role in collagen self-assembly, but it still largely unclear how water–collagen interactions influence the assembly process and determine fibril network properties. Here, we use H <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" overflow="scroll"> <mml:msub> <mml:mrow /> <mml:mn>2</mml:mn> </mml:msub> </mml:math> O/D O isotope effect on hydrogen-bond strength water investigate of hydration self-assembly. We dissolve D compare...
We report three families with arterial aneurysms and dissections in which variants predicted to be pathogenic were identified SMAD2. Moreover, one variant occurred de novo a proband unaffected parents. SMAD2 is strong candidate gene for given its role the TGF-β signaling pathway. Furthermore, although SMAD3 probably have functionally distinct roles cell signaling, they are structurally very similar. Our findings indicate that mutations associated accordance observation patients genes...
Abstract Ruptured abdominal aortic aneurysms (AAA) are associated with overall mortality rates up to 90%. Despite extensive research, mechanisms leading AAA formation and advancement still poorly understood. Smooth muscle cells (SMC) predominant in the medial layer maintain wall structure. Apoptosis of SMC is a well-known phenomenon pathophysiology AAA. However, remaining function less extensively studied. The aim this study assess vitro contractility human non-pathologic SMC. Biopsies were...
The tenascin‐X ( TNX ) deficient type Ehlers–Danlos syndrome EDS is similar to the classical of EDS. Because limited awareness among geneticists and challenge molecular analysis TNXB gene , ‐deficient probably be under diagnosed. We therefore performed an observational, cross‐sectional study. History physical examination were performed. Results serum measurements collected mutation was by a combination next‐generation sequencing NGS ), Sanger multiplex ligation‐dependent probe amplification...
Motile and non-motile cilia play critical roles in mammalian development health. These organelles are composed of a 1000 or more unique proteins, but their assembly depends entirely on proteins synthesized the cell body transported into cilium by intraflagellar transport (IFT). In mammals, malfunction due to IFT dysfunction results complex developmental phenotypes that affect most organs. contrast, disruption motile function causes subfertility, left-right axis, recurrent airway infections...
Background: Classical-like Ehlers Danlos Syndrome type 1 (clEDS1) is a very rare form of (EDS) caused by tenascin-X (TNX) deficiency, with only 56 individuals reported. TNX an extracellular matrix protein needed for collagen stability. Previous publications propose that clEDS1 might be at risk gastrointestinal (GI) tract perforations and/or tracheal ruptures. Aim: To characterize complications resulting from the GI rupture in international case series due to disease-related tissue fragility....
Solid tumors contain hypoxic regions in which cancer cells are often resistant to chemotherapy-induced apoptotic cell death. Therapeutic strategies that specifically target and promote apoptosis particularly appealing, as few normal tissues experience hypoxia. We have found the compound ABT-737, a Bcl-2 homology domain 3 (BH-3) mimetic, promotes death human colorectal carcinoma small lung lines exposed This induction of was mediated through downregulation myeloid leukemia sequence 1 (Mcl-1),...
An X-linked condition characterized by the combination of hypomyelinating leukodystrophy and spondylometaphyseal dysplasia (H-SMD) has been observed in only four families, with linkage to Xq25-27, recent genetic characterization two families a common AIFM1 mutation. In our study, 12 patients (6 families) H-SMD were identified underwent comprehensive assessment accompanied whole-exome sequencing (WES). Pedigree analysis all was consistent recessive inheritance. Presentation typically occurred...
We aimed to determine the diagnostic yield of a targeted-exome panel in cohort 74 Dutch primary ciliary dyskinesia (PCD) patients. The consisted 26 PCD-related and 284 candidate genes. To prioritize PCD genes, we investigated transcriptome human airway cells 12 healthy volunteers during vitro ciliogenesis hypothesized that genes show significant upregulation. compared gene expression epithelial precursor grown as collagen monolayer ciliated suspension by RNA sequencing. All reported...
Hyaluronan, a high molecular weight glycosaminoglycan is associated with cellular proliferation and migration. In number of different tumour types, there close correlation between progression hyaluronan production, either by the cells or surrounding stromal cells. We have examined ability an aggressive melanoma cell line (C8161) to stimulate synthesis fibroblast hyaluronan, association cell-surface CD44 receptors invasion. Melanoma cell-conditioned medium (CM) prepared in low glucose (1...
Background Missense variants in SMAD2 , encoding a key transcriptional regulator of transforming growth factor beta signalling, were recently reported to cause arterial aneurysmal disease. Objectives The aims the study identify genetic disease families with aortic/arterial and further define genotype–phenotype correlations. Methods results Using gene panel sequencing, we identified nonsense variant four missense variants, all affecting highly conserved amino acids MH2 domain. premature stop...
Introduction Bone biopsies have been obtained for many centuries and are one of the oldest known medical procedures in history. Despite introduction new noninvasive radiographic imaging techniques genetic analyses, bone still valuable diagnosis diseases. Advanced assessment quality biopsies, which emerged during last decades, allows in-depth tissue analyses beyond structural changes visible histology. In this review we give an overview application advantages advanced analysis clinical...