SLC13A5, neuronal citrate transport, and epileptic encephalopathies

TCA cycle. While most genetic epileptic encephalopathies are due to de novo mutations, there is increasing knowledge about epileptic encephalopathies due to recessive mutations, often with entirely unexpected mechanisms. In a recent publication in Brain, we were able to expand the phenotype of a neonatal epileptic encephalopathy due to a deficiency of the neuronal citrate transporter. Furthermore, in addition to GLUT1 deficiency and pyruvate dehydrogenase deficiency, SLC13A5 seems to be a third disease where the ketogenic diet may represent a causal treatment option. Continue reading

CHD2 – this is what you need to know in 2015

CHD2. Few genes have captured our attention over the last two years like CHD2 has. It is a gene that we almost missed, then sat on for more than a year since we didn’t believe it, only to realize in the end that it is a gene for a specific photosensitive epilepsy syndrome that many people had encountered, but that few people had a name for. Here is what you need to know about CHD2 in 2015. Continue reading

Weekly updates – KCNQ2, PCDH19, AES in Philly, STXBP1 awareness

Issue 15/2015. This week, I wanted to give a brief update on a few Epilepsiome genes and let you know about two upcoming meetings. Yes, we have not been very active on this blog for the last few weeks given that that I was on service at CHOP at the time. But we’re catching up and there are a few recent additions to KCNQ2, PCDH19, and STXBP1. This information will be added to the Epilepsiome pages with the next updates.

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The three twists in the SCN1A story that you didn’t know about

SCN1A. Finally, after various other epilepsy genes have been added, we are trying to put together a static website on SCN1A rather than updates only. SCN1A is by far the most prominent epilepsy gene and the first genetic etiology that comes to mind for anything relating to fever and seizures. While our Epilepsiome page will give you all the relevant facts regarding this gene, here is my personal view on the SCN1A story. Continue reading

Welcome to Rare Variant Island

Gamification. Genetic epidemiology is probably one of the driest and most boring fields of genome science that you will encounter. However, there are some basic questions that keep on puzzling me. One of them is about rare variants: if we think of rare variants that are present in patients, but also in controls, how could a combination of rare variants ever fully explain a disease? What are the rules, what are the conditions for such a situation? I happened to play around with R yesterday, and caught by a wave of gaming spirit, I wanted to try and see. I created a virtual population with 1 million people where disease risk is almost fully explained by 300 rare variants – a little genetic SimCity that I will call Rare Variant Island. Follow me through some of the adventures in our new empire and see what happens. Continue reading