PhD defence M. (Martijn) Baas

Congenital Upper Limb Anomalies vary in etiology and severity. To structure this spectrum, recently the Oberg, Manske and Tonkin classification was introduced. In the three parts of this thesis, we investigate the OMT classification itself, it’s use in population studies and the relation of this classification and the concordant classification strategy to the genetic substrate of the observed anomalies. In the first part of the thesis, we illustrate that all separate entities should be classified in order to relate the phenotype to the genotypes available in literature in  a tool called CulaPhen. Also we illustrate the loss of data if phenotypes are (wrongfully) taken together as one entity. 
The second part of the thesis further investigates the need of in-depth classification of CULA. In the two chapters we first illustrates that this registration aids to develop treatment protocols for patient with combined upper and lower limb anomalies. In the second chapter we illustrate that the in-depth classification allow to further study inheritance patterns of patients with triphalangeal thumbs. Lastly, part three describes phenotype to genotype correlation of CULA. We illustrate that patterns of CULA predict the location of the mutation in patients with GLI3-mediated polydactyly. Furthermore, based on the similarity of phenotypes, we were able to identify a new enhancer that causes TPT-polydactyly phenotypes. Lastly, we used our CulaPhen methodology in the analysis of NGS data of patients with radial longitudinal deficiency.

The public defence will take place at the Senate Hall, 1st floor Erasmus Building, location campus Woudestein. The ceremony will begin exactly at 10.30 AM. In light of the solemn nature of the ceremony, we recommend that you do not take children under the age of 6 to the first part of the ceremony.