Better genetic decoding of neurodevelopmental disorders

Two HUDERF patients with neurodevelopmental disorders (here cognitive and behavioral symptoms) showed partial loss (deletion) of the DLG2 gene, which plays an important role in the development, plasticity, and stability of synapses (the zone where two neurons touch each other allowing them to exchange information).

A research team led by Dr. Guillaume Smits, Nicolas Deconinck and Catheline Vilain of HUDERF and Professor Gianluca Bontempi of ULB (Machine Learning Group) collaborated through the Interuniversity Institute of Bioinformatics in Brussels, (IB) ², a joint research institute at the Université libre de Bruxelles (ULB) and the Vrije Universiteit Brussel (VUB). Together, they worked at integrating large genomic, epigenomic, transcriptomic and clinical datasets. The computational experiments, performed by Claudio Reggiani, a PhD student funded by the Belgian Kids' Fund for Pediatric Research and Innoviris, pinpointed two novel DLG2 promoters and coding exons conserved in human and mouse and present in the fetal brain. The deletion of these new regions were found statistically associated with developmental delay and intellectual disability in two independent patient cohorts, supporting the pathogenic role of these new elements into the neurodevelopmental symptoms of both HUDERF patients. The results of this work have been published in the international journal Genome Medicine and are presented in this video.

From a medical perspective, the findings will help medical doctors in improving future diagnosing of children with NDDs, intellectual disability, autism and schizophrenia. From a scientific point of view, this work shows how the in silico integration of multiple large datasets can bring knowledge about the genome. It also provides elegant progress into the molecular cause of neurodevelopmental disorders and improves fundamental knowledge about the DLG2 gene.