Dynamin 1, the synapse, and why epilepsy gene discovery is now officially over

E2 consortium. Infantile Spasms and Lennox-Gastaut Syndrome are two epilepsy syndromes with a strong genetic component. De novo mutations play an important role in genetic epilepsies. However, given the overall mutational noise in the human genome, telling causative genes from innocent bystanders is difficult. In the largest and most comprehensive analysis so far, our E2 consortium just published a joint analysis of 356 patient-parent trios, which were analyzed by exome sequencing. In addition to implicating DNM1, GABBR2, FASN, and RYR3, this publication sends a clear message: the age of gene discovery in epilepsy is over – from now on, genes will find themselves. Let me tell you what I mean by this. Continue reading

Publications and thoughts of the week – SUMO, SENP2, and data return from exome studies

This week. Because I was traveling this week, I didn’t manage to put a blog post together for you. However, I wanted to catch up with recent publications in the field. Also, I wanted to point out a recent trend in the field – emerging interest and concern about data return from next-generation sequencing studies. However, let’s start with this week’s publications. Continue reading

The 30-10 rule of clinical exome sequencing

30/10. The impact of whole exome sequencing (WES) on clinical management of patients with neurodevelopmental disorders can increasingly be felt, and overall numbers are emerging, which document the success and impact of this technology on clinical decision making. In 30% of patients with neurodevelopmental disorders, a diagnosis can be obtained through WES, and in 10% of patients, this diagnosis significantly alters patient management. A recent publication in Annals of Neurology investigates whether this concept extends beyond the epileptic encephalopathies and also includes patients with presumed cerebral palsy, cerebellar abnormalities, and hypomyelination. Continue reading