How do you feel as a Nobel laureate? For the few of us who aspire to be Nobel laureates one day, there is news for you. You already won it. The Nobel Peace Prize to the EU might not have been the award and format that you were initially thinking about, but despite all the hardships and difficulties that the life of a scientist puts you through, it is difficult to dismiss that the Europe we are working in right now is much different from the continent that our parents and grandparents knew. This became clear to me on my recent trip to Strasbourg. Continue reading
Category Archives: Opinion
De novo mutations in Infantile Spasms and Lennox-Gastaut Syndrome
Quantum leap. At the Annual Meeting of the American Epilepsy Society, the Epi4K consortium presented the first data on exome sequencing in epileptic encephalopathies. This data is the most exciting finding in the field of epilepsy genetics in 2012 so far, as it provides a deep insight into the genetic architecture of Infantile Spasms (IS) and Lennox-Gastaut Syndrome (LGS). With the findings presented by the Epi4K collaborators, the epileptic encephalopathies are joining a group of neurodevelopmental disorders with a significant burden of de novo mutations. However, there are important differences that set both IS and LGS apart from diseases like autism, intellectual disability and schizophrenia. Continue reading
Missed SCN1A mutations in Dravet Syndrome – a matter of degrees
Back from AES. I have just come back from the 66th Annual Meeting of the American Epilepsy Society and I would like to share some of the most recent findings that were presented at this meeting. Since we felt that our presentation on the “re-discovery” of SCN1A mutations in SCN1A-negative patients with Dravet Syndrome received quite some attention, I thought that I would share this part of our presentation as a brief screencast. In particular, I would like to thank Anna-Kaisa Anttonen and Anna-Elina Lehesjoki for providing us with the trace files. And of course thanks to everybody in RES who was involved in this.
How to deal with scientific disappointment
Difficult times. The last two weeks were hard for me scientifically. In addition to having two papers rejected within a week, I learned that a major grant proposal that was rejected. Particularly the latter I didn’t take well, since I was quite convinced that we would make the next round. Also, this was for a project where funding was more than necessary. We all know scientific disappointments in their various forms, and I thought that I would dedicate a post to this topic. Please follow me while I stumble through the internet, looking for the science of disappointment. Continue reading
Of diapers and desktops – a belated Thanksgiving post
The post I didn’t write. Last Thursday was Thanksgiving and my daughter’s second birthday. Therefore, even though I initially had grandiose plans for a Thanksgiving post, I did what a family father would do on days like this – not write blog posts. Therefore, having digested the Thanksgiving dinner and having survived Black Friday, here comes our belated Thanksgiving post. Let’s think for a second how we handle the combination of family and research. Continue reading
Validation of rare variants – the power of finding anything at all
How much? Last week, we discussed the probability of finding de novo variants in patients with epileptic encephalopathies, but our calculations were only half the story. Genes that are identified through genome-wide sequencing technologies are often validated in additional cohorts. In many cases, we will only be able to establish a given gene as causative if we find another patient with a mutation in this gene. I was therefore asked to write an additional post on power calculations for rare variants in validation cohorts. Let me tell you the story how I stumbled across a little bit of almost forgotten high school math. Continue reading
CACNA1A variants as genetic modifiers in Dravet Syndrome
Genetic modifiers. Dravet Syndrome, formerly Severe Myoclonic Epilepsy of Infancy (SMEI) is a severe epileptic encephalopathy starting in the first year of life. More than 80% of cases of Dravet Syndrome are caused by loss-of-functions mutations in SCN1A, a voltage-gated sodium channel predominantly expressed on GABAergic interneurons. Now, a recent paper in Neurobiological Disorders investigates the role of CACNA1A variants as possible genetic modifiers in Dravet Syndrome. Continue reading
Exome sequencing in epileptic encephalopathies – the powers that be
The power, over and over again. I must admit that I am thoroughly confused by power calculations for rare genetic variants, particularly for de novo variants that are identified through trio exome sequencing. Carolien has recently written a post about the results we can expect from exome sequencing studies. For a current grant proposal, I have now tried to estimate the rate of de novos using a small simulation experiment. And I have realized that we need to re-think the concept of power. Continue reading
Traveling with Lennox – myoclonic jerks, West Syndrome and the 34th meridian
Where is West Syndrome? Earlier this week while browsing through the contents of Lennox’s book, I wondered where his description of West Syndrome was hidden. Lennox is very careful in reviewing the historical data on epilepsy, but for some reason, he did not mention the report by William James West, who described a particular type of epilepsy in his own son that would later be named after him. Then, when I had almost forgotten that I was on the lookout for West Syndrome, I stumbled upon it in the chapter on myoclonic seizures. Continue reading
Traveling with Lennox – the petit mal triad
Lights on and lights out. Staring spells, petits mals, pyknolepsy and absence seizures. The brief spells that occur in patients with epilepsy have riddled neurologists for centuries. This became clear to me when Zaid Afawi and myself saw an epilepsy family in the West Bank on Sunday. When are staring spells epileptic and what kind of seizures are they? For me, this was a good opportunity to read Lennox’s thoughts on this. Eventually, after a long day under the Middle Eastern sun, I fell asleep over the chapter on absence status. Continue reading