Research team
The Belgian prenatal microarray database (BEMAPRE): realization of the database, determination of genotype-phenotype correlations and postnatal follow-up.
Abstract
In Belgium, samples for prenatal genetic diagnosis are analyzed by Chromosomal Microarray Analysis (CMA). The main challenge herein lies in the interpretation of copy number variants (CNVs) for which knowledge about postnatal outcome is limited. All Belgian genetic centers have agreed on prenatal CNV classification, but ambiguous situations still occur. The goal of our research is to 1) investigate genotype-phenotype correlations using clinical data of children with prenatally registered non-benign CNVs; 2) narrow down the prenatal genotype-phenotype correlation of frequently found known pathogenic CNVs and 3) focus on outcome in children with other than benign CNVs and renal/urogenital anomalies on ultrasound. To secure our goals, we have created a Belgian database for registration of prenatal CMA data. In the first year of my PhD, I developed the framework of this database, guided the genetic centers in importing their data and presented our first results at international conferences. Next, I will start postnatal data collection of children with other than benign CNVs, determine renal function at the age of 1 year in case of a renal/urogenital ultrasound anomaly, and assess neurologic and psychomotor development at the age of 2-3 years. By ameliorating genotype–phenotype knowledge of prenatally registered CNVs, we will develop a strong scientific base for clinical decision-making in prenatal diagnosis. This work is a collaboration of all Belgian academic genetic centers.Researcher(s)
- Promoter: Jacquemyn Yves
- Co-promoter: Blaumeiser Bettina
- Co-promoter: Janssens Katrien
- Fellow: Muys Joke
Research team(s)
Project type(s)
- Research Project
In vivo modelling of two ulcero-mutilating neuropathies in Drosophila melanogaster
Abstract
The aim of this project is to develop fruit fly models of two phenotypically similar neurodegenerative disorders of the peripheral nervous system, Charcot-Marie-Tooth type 2B and Hereditary Sensory Neuropathy type I. The wild-type and mutant versions of the responsible genes, RAB7 and SPTLC2, will be expressed in Drosophila melanogaster. This will allow us to investigate the pathomechanism of both diseases in great detail and to investigate the possibility of a shared etiology for both disorders. Moreover, the fly models can serve as screening platforms for therapeutic compounds.Researcher(s)
- Promoter: Janssens Katrien
Research team(s)
Project type(s)
- Research Project
VIB-Identification of common molecular mechanisms in the hereditary sensory neuropathies.
Abstract
This project aims to model Chacot-Marie-Tooth type 2B (CMT2B) and hereditary sensory and autonomic neuropathy type I (HSAN-I) mutations into Drosophila.Researcher(s)
- Promoter: Timmerman Vincent
- Co-promoter: Janssens Katrien
Research team(s)
Project type(s)
- Research Project
Functional consequences of RAB7 mutations in the pathogenesis of an ulcero-mutilating neuropathy.
Abstract
This postdoctoral research project aims at unravelling the pathogenesis of two ulcero-mutilating neuropathies, Charcot-Marie-Tooth 2B and Hereditary Sensory Neuropathy type I. The neuropathies show strong phenotypical similarities, but are caused by mutations in 2 different genes, respectively RAB7 and SPTLC1. Using primary sensory neurons, isolated from rat embryos and virally transduced with wild-type or mutant constructs, I will study the effect of the mutations on e.g. the endosomal population, lipid raft formation and axonal transport. Moreover, I will make a Drosophila model of both disorders, which will allow me to investigate how the mutations affect the peripheral nervous system in vivo and will help me to try to correlate the pathomechanisms of these two neuropathies.Researcher(s)
- Promoter: Timmerman Vincent
- Fellow: Janssens Katrien
Research team(s)
Project type(s)
- Research Project
VIB-Functional consequences of RAB7 mutations in the pathogenesis of an ulcero-mutilating neuropathy.
Abstract
Researcher(s)
- Promoter: Timmerman Vincent
- Fellow: Janssens Katrien
Research team(s)
Project type(s)
- Research Project
Further characterisation of the role of TGF-beta1 in bone metabolism and identification of currently unknown genes involved in osteoblast differentiation.
Abstract
This research project aims at identifying new genes involved in osteoblast differentiation, but also builds on the functional TGF-b1 studies performed during my PhD. The first goal will be achieved by performing a functional screen with a siRNA library: selective knock-down of genes that are possibly involved in the differentiation of osteoblast precursors, can identify those genes that influence this process. Our second goal will be to answer some of the remaining questions regarding signaling by TGF-b1 mutant proteins. Points to investigate are: Demonstration of the presence of an intracrine signaling pathway, for which we find indication in the signaling mode of type 2 mutants; Construction of a knock-in mouse model for in vivo and in vitro studies of the functioning of mutant TGF-b1 in bone metabolism; Look into the role of the latent TGF-b binding protein (LTBP) in the phenotypic manifestation of the mutations.Researcher(s)
- Promoter: Van Hul Wim
- Fellow: Janssens Katrien
Research team(s)
Project type(s)
- Research Project
Identification and characterisation of a gene responsible for the hyperostosis of Camurati-Engelmann.
Abstract
Camurati-Engelmann disease is a rare disease with an autosomal dominant inheritance. It is characterized by progressive hyperostosis of the long tubular bones. Severe cases also show hyperostosis of skull and vertebrae. The main clinical features are muscle weakness, a waddling gait and severe pain in the legs. Until now, the localisation of the responsible gene and the underlying pathogenetic mechanism are unknown. It is our aim to clarify this by positional cloning. In a first phase, we started a genomewide search on an large Israeli family.Researcher(s)
- Promoter: Van Hul Wim
- Fellow: Janssens Katrien
Research team(s)
Project type(s)
- Research Project
Identification and characterisation of a gene responsible for the hyperostosis of Camurati-Engelmann.
Abstract
Camurati-Engelmann disease is a rare disease with an autosomal dominant inheritance. It is characterized by progressive hyperostosis of the long tubular bones. Severe cases also show hyperostosis of skull and vertebrae. The main clinical features are muscle weakness, a waddling gait and severe pain in the legs. Until now, the localisation of the responsible gene and the underlying pathogenetic mechanism are unknown. It is our aim to clarify this by positional cloning. In a first phase, we started a genomewide search on an large Israeli family.Researcher(s)
- Promoter: Van Hul Wim
- Fellow: Janssens Katrien
Research team(s)
Project type(s)
- Research Project
Identification and characterisation of a gene responsible for the hyperostosis of Camurati-Engelmann.
Abstract
Camurati-Engelmann disease is a rare disease with an autosomal dominant inheritance. It is characterized by progressive hyperostosis of the long tubular bones. Severe cases also show hyperostosis of skull and vertebrae. The main clinical features are muscle weakness, a waddling gait and severe pain in the legs. Until now, the localisation of the responsible gene and the underlying pathogenetic mechanism are unknown. It is our aim to clarify this by positional cloning. In a first phase, we started a genomewide search on an large Israeli family.Researcher(s)
- Promoter: Van Hul Wim
- Fellow: Janssens Katrien
Research team(s)
Project type(s)
- Research Project