Research topics

The research focus of MEDGEN can broadly be defined as the elucidation of the genetic mechanisms causing congenital anomalies and heritable connective tissue disorders with focus on cardiovascular, growth and osteoarticular diseases.

More specifically we are currently focusing on the following topics:

Growth disorders, short stature syndromes and skeletal dysplasias

Prinicipal Investigator: Geert Mortier

General goals for this research line are:

- to identify genes that are important in the regulation of linear growth, endochondral
- to explore the phenotypic consequences of mutations in these genes
- to gain more insights in the pathophysiology and genotype-phenotype correlations in these disorders.

Major research accomplishments in the past:
- identification of the causal genes for acrocapitofemoral dysplasia (IHH), osteopoikilosis (LEMD3), the Buschke-Ollendorff syndrome (LEMD3), Czech dysplasia (COL2A1) and spondylo-megaepiphyseal-metaphyseal dysplasia (NKX3-2).
- study of type 2 collagen disorders with in-depth analysis of genotype-phenotype correlations; construction of growth charts for SEDC
- delineation of a new microdeletion syndrome on 12q14 characterized by the association of short stature, cognitive defects and osteopoikilosis

Current research topics:
The major topics of our current research are the following:
- The identification of the genetic defect causing sporadic melorheostosis.
- We have been collecting some unique families with a skeletal dysplasia for which the genetic defect is still unknown. We aim to unravel the genetic cause by applying  whole exome sequencing in these families
- The elucidation of the genetic causes of carpal tunnel syndrome
- Identification of new genetic mutations and epigenetic alterations in children with unexplained growth failure

Cardiovascular genetics

Principal Investigator: Bart Loeys and Lut Van Laer

General goals for this research line are:

  • To identify genes that are associated with thoracic aortic aneurysms and dissections;
  • to explore the phenotypic consequences of mutations in these genes;
  • to gain more insights in the pathophysiology and genotype-phenotype correlations in these disorders;
  • to develop next generation sequencing gene panels for Sudden Cardiac Death.

Major research accomplishments in the past:
Delineation of a new syndrome, designated the Loeys-Dietz syndrome (LDS), and the identification of the causal genes (TGFBR1 for LDS1, TGFBR2 for LDS2, SMAD3 for LDS3, TGFB2 for LDS4, TGFB3 for LDS5)
Identification of the causal genes for Shprintzen-Goldberg syndrome (SKI), the Stiff Skin Syndrome (FBN1), Gray Platelet Syndrome (GFI1B), lethal myopathy and encephalopathy (IBA57), interstitial kidney disorder associated with anemia and growth retardation (SEC61A1)
Development of a next generation sequencing gene panel to improve the molecular diagnosis for thoracic aortic aneurysms and dissections

Current research topics:
Identification of novel genes responsible for the development of thoracic aortic aneurysms and dissections, both syndromic and non-syndromic types. Read more about aortic dissection (pdf - 13Kb).
Identification and characterisation of the genes associated with bicuspid aortic valve associated aortopathy. Read more about bicuspid aortic valve (pdf - 174Kb).
Development of a next generation sequencing gene panel to improve the molecular diagnosis for primary electrical disorders. Read more about sudden cardiac death (pdf - 175 Kb).
Application of next generation sequencing for the discovery of genes underlying rare monogenic disorders.

Hereditary bone tumours

Principal Investigator: Wim Wuyts

Osteochondromas are the most frequent hereditary bone tumours in children. Multiple osteochondromas (MO) is an autosomal dominant disorder characterized by the presence of many osteochondromas, often accompanied by skeletal deformities. In addition, MO patients have an increased risk for the development of chondrosarcomas.

Mutations in the EXT1 or EXT2 gene have been shown to be responsible for the osteochondroma development, but the mechanism(s) leading to chondrosarcoma transformation of an osteochondroma are poorly understood.

General goals for this research line are:
- Clinical end genetic characterization of MO
- Identification of genes and mechanisms leading to chondrosarcoma development

Major research accomplishments in the past:
- Identification of the MO causal gene EXT2
- Identification of the EXTL(like) genes (EXTL2, EXTL3)
- Determination of the MO mutation spectrum
- Genotype/phenotype studies of MO
- Development of diagnostic protocols for EXT1/EXT2 analysis

Current research topics:
- MO genotype-phenotype correlation studies
- Identification of chondrosarcoma causing genetic events

Adams-Oliver syndrome

Principal Investigator: Wim Wuyts

Adams-Oliver syndrome (AOS) is a hereditary disorder characterized by terminal limb defects, aplasia cutis and skull defects. Both autosomal dominant and recessive forms have been described and the disorder has been shown to be genetically heterogeneous.

General goals for this research line are:

  • Identification of genes causing AOS
  • Elucidation of the pathway(s) involved in AOS

Major research accomplishments in the past:

  • Identification of the AOS causing gene ARHGAP31

Current research topics:

  • Identification of MO causing genes
  • AOS genotype-phenotype studies