“In this month’s issue of the Journal of Human Genetics, Prof. Raoul Hennekam (PI at AMC) co-authors a publication which links different classes of dominantly acting mutations of CDC42, a master regulator of actin cytoskeleton and major node in intracellular signaling, to a heterogeneous set of developmental and multi-system phenotypes, demonstrating the critical requirement of proper CDC42 function in a large array of developmental processes.
This study exemplifies current challenges in syndrome delineation in the post-WES era and emphasizes the relevance of functional profiling in syndrome recognition and delineation. Thus if one works from 'gene-first' one may detect a relatively large group of affected individuals with a variant in the same gene, and that one can subgroup these individuals based on clinical findings, while without knowing that these patients belong to one another one would never have been possible to do so. The clinical subgroups fit in nicely with the variation in disturbances in functions that the produced protein has. In fact this way three new and allelic disorders have been defined. Likely in this way new entities will progressively be defined.”
See also Raoul Hennekam on youtube: https://www.youtube.com/watch?v=u7_nlX7J0bM
Download Martinelli report:
The American Journal of Human Genetics 102, 309–320, February 1, 2018