Developmental Genetics

Principal investigator
Prof.dr. Dorien Peters

Single gene defects contribute to a significant proportion of mortality, disability and disease. Research in this section aims to get insight into the genetic, pathophysiologic and functional mechanisms of inherited and inborn errors of human development and differentiation.

Research in this section involves two different topics:

1). Defects in renal development and differentiation -
      Polycystic Kidney Disease (PKD)

2). Defects in chromatin remodelling -
      Malformation/Mental retardation syndromes 


1). Defects in renal development and differentiation -
     Polycystic Kidney Disease (PKD)

Renal cystic disease encompasses a broad spectrum of hereditary, nonhereditary, and acquired conditions and is a common cause of renal failure. Our department focuses on the understanding of the pathophysiological mechanisms underlying Polycystic Kidney Disease, which is a systemic disorder with extra-renal manifestations such as hypertension, formation of cerebral and aortic aneurysms and formation of cysts in liver and pancreas.

Our research is aimed at fully understanding the pathogenesis of the disease, which must lead to the design of new therapeutic approaches. We utilize tools in genetics, molecular cell biology and pathology to  study three interrelated research topics: 1) Genetic studies and biomarkers. 2) Clarifying disease mechanisms using state-of-the art technologies 3) Identifying new drug targets and test new treatment strategies for PKD.

Genetic studies and biomarkers

Targeted and Next Generation Sequencing are being applied to get insight into the mutation spectrum and to identify novel and modifying genes. Metabolomic/proteomic profiling approaches are applied to identify and validate new tools to predict and monitor disease progression.

Clarifying disease mechanisms using state-of-the art technologies

We have generated a variety of (conditional) model systems and cell lines to get insight in the crucial initial pathogenic events and secondary effects of disturbed Pkd1 -gene expression, leading to cystogenesis and blood vessel abnormalities.

Identifying new drug targets and test new treatment strategies for PKD

Targeted analyses as well as high-throughput drug screenings using organoids are among the approaches to identify potential therapeutic targets. These are multidisciplinary programs in collaboration with bioinformaticians, chemo-informaticians, clinicians and toxicologists.

2). Defects in chromatin remodelling -
     Malformation/Mental retardation syndromes

In addition to structural and numerical variations of the genome, also point mutations can cause a wide variety of Malformation/Intellectual disability syndromes. In close collaboration with the Department of Clinical Genetics we apply a variety of molecular and genomics technologies to identify the causative genes and study the molecular defects. Our special interest are chromatin remodelling disorders including the Rubinstein-Taybi Syndrome, Coffin–Siris syndrome and the immunodeficiency, centromeric region instability, and facial anomalies syndrome (ICF).

Malformation/Mental retardation syndromes

Translocations, micro-deletions and duplications but also point mutations are the cause of a large number of malformation / mental retardation syndromes.
The Rubinstein-Taybi Syndrome (RSTS) is characterized by mental retardation, growth retardation, facial dysmorphology as well as broad thumbs and big toes. In addition, patients have an increased susceptibility for certain forms of cancer and massive keloid formation. Mutations in the genes encoding the transcriptional co-activators CREBBP and p300 account for the syndrome in 50% of the patients. These proteins are also Histone Acetyl Transferases and we have shown that loss of this HAT activity is sufficient to account for the phenomena seen in Rubinstein-Taybi patients. To further understand the etiology of RSTS and its associated complications, and to get insight in the origin of other malformation/mental retardation syndromes we are using a variety of (high resolution) methods and molecular cloning techniques to uncover the causative genes, study the functional consequences of mutations, perform genotype-phenotype analyses and identify down-stream targets.