A5086503100- Connective tissue disorders research
- Bone and Dental Protein Studies
- Cell Adhesion Molecules Research
- Wnt/β-catenin signaling in development and cancer
- Dermatological and Skeletal Disorders
- Ubiquitin and proteasome pathways
- Cellular transport and secretion
- Retinal Diseases and Treatments
- Skin and Cellular Biology Research
- Retinal Imaging and Analysis
- Collagen: Extraction and Characterization
- Protease and Inhibitor Mechanisms
- Proteoglycans and glycosaminoglycans research
- Bone health and treatments
- Genetic and Kidney Cyst Diseases
- Ophthalmology and Visual Impairment Studies
- Neurological diseases and metabolism
- Retinal Development and Disorders
- Lipid metabolism and biosynthesis
- Neurogenetic and Muscular Disorders Research
- Vitamin K Research Studies
- Connexins and lens biology
- Vascular Malformations and Hemangiomas
- RNA regulation and disease
- Bone health and osteoporosis research
Ghent University Hospital
2015-2023
The type I collagenopathies are a group of heterogeneous connective tissue disorders, that caused by mutations in the genes encoding collagen and include specific forms osteogenesis imperfecta (OI) Ehlers-Danlos syndrome (EDS). These disorders present with broad disease spectrum large clinical variability which underlying genetic basis is still poorly understood. In this study, we systematically analyzed skeletal phenotypes set zebrafish, diverse collagen, representing different human OI,...
ABSTRACT Whereas the vast majority of osteogenesis imperfecta (OI) is caused by autosomal dominant defects in genes encoding type I procollagen, mutations a myriad affecting procollagen biosynthesis or bone formation and homeostasis have now been associated with rare recessive OI forms. Recently, homozygous compound heterozygous BMP1, metalloproteases morphogenetic protein-1 (BMP1) its longer isoform mammalian Tolloid (mTLD), were identified 5 children severe form 4 individuals mild to...
Proteoglycans are among the most abundant and structurally complex biomacromolecules play critical roles in connective tissues. They composed of a core protein onto which glycosaminoglycan (GAG) side chains attached via linker region. Biallelic mutations B3GALT6, encoding one region glycosyltransferases, known to cause either spondyloepimetaphyseal dysplasia (SEMD) or severe pleiotropic form Ehlers–Danlos syndromes (EDS). This study provides clinical, molecular biochemical data on 12...
ABSTRACT TANGO1 (transport and Golgi organization‐1 homolog) encodes a transmembrane protein, which is located at endoplasmic reticulum (ER) exit sites where it binds bulky cargo, such as collagens, in the lumen recruits membranes from ER‐Golgi intermediate compartment (ERGIC) to create an export route for cargo secretion. Mice lacking Mia3 (murine orthologue) show defective secretion of numerous procollagens lead neonatal lethality due insufficient bone mineralization. Recently, aberrant...
Abstract Osteogenesis imperfecta (OI) is a genetically and clinically heterogeneous disorder characterized by bone fragility reduced mass generally caused defects in type I collagen structure or proteins interacting with processing. We identified homozygous missense mutation SEC16B child vertebral fractures, leg bowing, short stature, muscular hypotonia, densitometric histomorphometric features keeping OI distinct ultrastructural features. In line the putative function of as regulator...
The cyclic adenosine monophosphate responsive element binding protein 3-like 1 (CREB3L1) gene codes for the endoplasmic reticulum stress transducer old astrocyte specifically induced substance (OASIS), which has an important role in osteoblast differentiation during bone development. Deficiency of OASIS is linked to a severe form autosomal recessive osteogenesis imperfecta (OI), but only few patients have been reported. We identified first homozygous pathogenic missense variant...
Osteogenesis imperfecta (OI) is a heritable connective tissue disorder, mainly characterized by bone fragility and low mass. Defects in the type I procollagen‐encoding genes account for majority of OI, but increasingly more rare autosomal recessive (AR) forms are being identified, which caused defects involved collagen metabolism, mineralization, or osteoblast differentiation. Bi‐allelic mutations WNT1 have been associated with form AR severe osteoporosis, vertebral compression, scoliosis,...
Inactivating variants in the centrosomal CEP78 gene have been found cone-rod dystrophy with hearing loss (CRDHL), a particular phenotype distinct from Usher syndrome. Here, we identified and functionally characterized first missense variant c.449T>C, p.(Leu150Ser) three CRDHL families. The was biallelic state two Belgian families compound heterozygous state-in trans c.1462-1G>T-in third German family. Haplotype reconstruction showed founder effect. Homology modeling revealed detrimental...
Abstract Biallelic MFSD8 variants are an established cause of severe late‐infantile subtype neuronal ceroid lipofuscinosis (v‐LINCL), a lysosomal storage disorder, but have also been associated with nonsyndromic adult‐onset maculopathy. Here, we functionally characterized two novel found in child juvenile isolated maculopathy, order to establish refined prognosis. ABCA4 locus resequencing was followed by the analysis other inherited retinal disease genes whole exome sequencing (WES)....
Heat shock protein 47 (HSP47), encoded by the SERPINH1 gene, is a molecular chaperone essential for correct folding of collagens. We report homozygous p.(R222S) substitution in HSP47 child with severe osteogenesis imperfecta leading to early demise. p.R222 highly conserved residue located within collagen interacting surface HSP47. Binding assays show significantly reduced affinity HSP47-R222S type I collagen. This altered interaction leads posttranslational overmodification procollagen...
The bone disorder osteogenesis imperfecta (OI) is genetically heterogeneous. Most affected individuals have an autosomal dominant caused by heterozygous variants in either of the type I collagen genes (COL1A1 or COL1A2). To date, two reports linked Mesoderm Development LRP Chaperone (MESD) to recessive OI XX. Four different biallelic pathogenic MESD were shown cause a progressively deforming phenotype, associated with recurrent fractures and oligodontia five families. Recently, compound...
Abstract Fungal infections, ranging from superficial to life-threatening represent a major public health problem that affects 25% of the worldwide population. In this context, study host-pathogen interactions within host is crucial advance antifungal therapy. However, since fungal cells are usually outnumbered by cells, transcriptome frequently remains uncovered. We compared three different methods selectively lyse human in vitro mixes, composed Candida and peripheral blood mononuclear...
SNARE proteins comprise a conserved protein family responsible for catalyzing membrane fusion during vesicle traffic. Syntaxin18 (STX18) is poorly characterized endoplasmic reticulum (ER)-resident t-SNARE. Recently, together with TANGO1 and SLY1, its involvement was shown in ER to Golgi transport of collagen II chondrogenesis. We report fetus severe osteochondrodysplasia whom we identified homozygous substitution the highly p.Arg10 Pro STX18. CRISPR/Cas9-mediated Stx18 deficiency zebrafish...
ABSTRACT The type I collagenopathies are a group of heterogeneous connective tissue disorders, that caused by mutations in the genes encoding collagen and include specific forms Osteogenesis Imperfecta (OI) Ehlers-Danlos syndrome (EDS). These disorders present with broad disease spectrum large clinical variability which underlying genetic basis is still poorly understood. In this study, we systematically analyzed skeletal phenotypes set zebrafish, diverse collagen, representing different...