The sugar code. Many proteins in the human body undergo post-translational modification. A common mechanism to modify the function of proteins is a process called glycosylation, the adding of carbohydrate residues to protein. Glycosylation is probably the most complex post-translational modification, critically important to various physiological functions and therefore tightly regulated in cells. Accordingly, genetic disorders that interfere with glycosylation may present as severe, multisystem disorders. However, it is increasingly recognized that many congenital disorders of glycosylation have an exclusively neurological phenotype. Here is an update on ALG13 epileptic encephalopathy, a recently identified disease entity that may account for up to 2% of Infantile Spasms in females. Continue reading
Issue 8/2015. This week’s review of the relevant publications in the field is about a novel risk factor for focal epilepsies, a gene involved in mRNA transport from the cell nucleus, and a small, confirmatory study on exome sequencing in Infantile Spasms.
Issue 5/2015. Each of these three genes may ring a bell, but the context in which they were described this week is new. Here is our overview of some of the most relevant publications this week. Continue reading
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
This week in epilepsy genetics. The following publications might be relevant for you, as they demonstrate what happened in the field of epilepsy genetics in the last two weeks. The publications range from basic science studies in extracellular space to novel gene discoveries. I have added a brief comment to each of these studies. Continue reading
The de novo paradigm. De novo mutations play a significant role in many neurodevelopmental disorders including autism, intellectual disability and schizophrenia. In addition, several smaller studies have indicated a role for de novo mutations in severe epilepsies. However, unless known genes for human epilepsies are involved, findings from large-scale genetic studies are difficult to interpret. De novo mutations are also seen in unaffected individuals and only very few genes are observed more than once. Now, a publication in Nature by the Epi4K and EPGP collaborators uses a novel framework to tell pathogenic mutations from genomic noise. Their study provides very strong evidence for a predominant role of de novo mutations in Infantile Spasms and Lennox-Gastaut Syndrome. Continue reading