The novel gene dilemma

N-of-1. The use of whole exome sequencing has led to many of the recent genes discovered in the epilepsy field. However, in contrast to established genes or emerging genes that are found in several patients, there is a significant proportion of patients who carry de novo mutations in novel genes. In many cases, these novel genes look very suspicious. One aspect of a recent publication in Genetics in Medicine was to assess how these suspicious candidates convert to established genes over time. Continue reading

My name is Jonas – a blizzard blog post

Do you want to build a snowman? During this weekend, winter storm Jonas descended upon the Eastern United States. Delaware County became covered under about two feet of snow, basically shutting down public life in the Philadelphia and the surrounding suburbs. Being trapped in the house with the kids exhausted from playing outside gave me the opportunity to catch up on my blogging duties and to engage in creative writing. Besides a reference to the 1994 Weezer alternative rock anthem, here is what snow storm Jonas told me about science. Continue reading

This is what you need to know about PRRT2 in 2016

PRRT2. Finally, in 2016, I have managed to put a blog post together on the most common gene for benign epilepsies in the first year of life. Even though the PRRT2 gene was only discovered in 2011, it has become the most common cause of self-limiting infantile epilepsies. Despite its prominent role in human disease, the function of the PRRT2 protein remains unclear and it is assumed that it plays an important role in the presynapse. Here is what we know about PRRT2 in 2016. Continue reading

Areas of uncertainty – an unusual introduction to 2016

Happy 2016. Talking about things we don’t know or are not sure about may be a strange introduction to a new year that is full of promises for the field of epilepsy genetics. However, there were two questions during the holidays that carried over from 2015 into the new year that I didn’t know the answer to and that we repeatedly discussed in our group. Two relatively simple questions: Can we give lamotrigine to a patient with GEFS+ -not Dravet Syndrome– and a mutation in SCN1A? Should we withhold valproic acid from a patient with a single POLG mutation identified through diagnostic gene panel? You feel that you know the answer to these questions, but what is actual data and what is only inference? Follow me through a brief discussion on why we need to be careful when it comes to claiming knowledge that we don’t really have yet. Continue reading