Over the past 10 years, our purpose has been to gain insight into the mechanisms leading to DBD. Thanks to our close links with the departments of Genetics, Neurology, Neuroradiology, Pediatrics and Child Psychiatrics at Necker as well as several reference centers, an ever-expanding collection of patients with unsolved neurodevelopmental diseases is being recruited. These patients are the corner stone of our studies. In addition, the local environment and context are both extremely relevant and efficient, with access to crucial platforms and core facilities for research including genomics, single-cell, imaging, induced pluripotent stem cells (iPSCs), bioinformatics, and animal models (mouse, and zebrafish). Lastly, our work relies on strong national and international collaborations with laboratories providing expertise in neurobiology, glycobiology, electrophysiology and bioinformatic analyses. The lab activities can be separated into three topics with a lot of cross-talks between each: (1) human genetic research projects; (2) basic science research projects and (3) transfer of knowledge to the diagnostic lab. The first topic is dedicated to the identification of new genetic defects involved in DBD with direct consequences on patients’ molecular diagnosis. The second aims to better understand normal brain development by dissecting disease mechanisms. For this aim, we focused mostly on DBD with structural cerebellar defect (SCD) to develop our own models. The last topic includes the development of improved diagnosis strategies using new sequencing or bioinformatic approaches.

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