Systematic Gene Identification in ARM and EEC

The current knowledge of the genetic factors underlying the development of uro-rectal malformations and the exstrophy-epispadias complex is very limited. Since these malformations are associated with reduced reproduction it is reasonable to assume that in a significant proportion of patients the resultant phenotype is caused by new mutations (de novo mutations). We will use a chip-based genome-wide approach to systematically search for new mutations characterized by a loss or gain of genomic material. The study sample will comprise 100 ARM and 100 EEC patients characterized by a negative family history and a severe expression of the phenotype. The parallel investigation of the patients' parents will allow the identification of de novo mutations in a highly efficient manner.

The causative genes residing in the newly implicated genomic regions will be identified by a combination of expression data, sequencing information from independent patients and transgenic mouse studies. Close interaction with other projects from the network will be crucial for performing these experiments.

It is expected that the identification of the causative genes and the involved biological pathways will lead to a profound understanding of the molecular biology mechanisms of normal and disturbed embryonic development of the human urogenital and rectal system. Furthermore, the identification of high-penetrance causative genes will immediately lead to the establishment of new diagnostic possibilities, serving the families with a better knowledge about the causes of the disorder and a precise estimation of recurrence risks.

Project Leaders

Further Cooperators

Dipl. ökotroph. Markus Draaken

Per Hoffmann

Cand. med. Friederike Baudisch

Cand. med. Charlotte Schramm

Cand. med. Lisa Gambhir