Evidence and absence. There is a time before and after ExAC, the gigantic variant repository based on more than 60,000 exomes sequenced at the Broad Institute. ExAC was released in October 2014 and has suddenly provided the community with access to variant data of roughly ten times more individuals than previous resources. But what happens when you check variants that were previously considered pathogenic and they are seen at low frequency in ExAC? Welcome to the Zero ExAC problem, providing us with a taste of the complications that epilepsy gene variant interpretation will face in the future. Continue reading
Monthly Archives: September 2015
TBC1D24 – this is what you need to know in 2015
The TBC1D24 story. Mutations in TBC1D24 were found initially in two recessive families with different types of epilepsy in 2010. This was followed by the identification of mutations in another recessive epilepsy family in 2013, and then by the identification of 9 families with mutations and DOORS syndrome (Deafness, Onycho-Osteodystrophy, mental Retardation and Seizures). Surprisingly, TBC1D24 mutations were then also identified in families with autosomal dominant or recessive non-syndromic deafness without epilepsy. Continue reading
These are the 78 genes involved in human epilepsy – a survey
Questionnaire. This week we have a huge favor to ask from you. We need your input on our Epilepsiome project. Please help us prioritize the 60-80 genes that will be part of our ongoing gene review effort. Help us build the Epilepsiome. Your input is needed. Continue reading
PRIMA1 mutations in recessive frontal lobe epilepsy
Acetylcholine. The success story of identifying epilepsy genes started with familial frontal lobe epilepsies and the discovery of CHRNA4, coding for a subunit of the nicotinergic acetylcholine receptor. Ever since this initial discovery, other gene identifications have reinforced a dysfunction in cholinergic signaling as one of the key mechanisms in genetic frontal lobe epilepsies. A recent study in the Annals of Clinical and Translational Neurology now identifies a novel gene for familial frontal lobe epilepsies, coding for an anchoring protein for acetylcholinesterase (AChE), the key enzyme breaking down acetylcholine. Continue reading
CACNA1A – this is what you need to know in 2015
P/Q. This week’s gene of the week is an atypical epilepsy gene, which is the main reason that this post is only coming out on Friday rather than Monday. Even though I was initially highly motivated to put something together on CACNA1A, I soon discovered that this gene is overwhelming. CACNA1A is a gene for both a channelopathy and trinucleotide repeat disorder, a gene for early childhood-onset and late onset adult neurological disorders, and a gene responsible for both episodic neurological conditions and neurodegenerative diseases. I have tried to put this into a coherent format. Here is what you need to know about CACNA1A in 2015. Continue reading
Publications of the week – SCN1A in encephalopathy after febrile seizures, SLC12A5/KCC2 in MMPSI
Issue 14/2015. This week’s publications of the week are about a novel phenotype consisting of persistent encephalopathies with MRI findings associated with SCN1A and SCN2A mutations, a novel gene for Malignant Migrating Partial Seizures of Infancy (MMPSI). Continue reading
Here are the three things the beach told me about science
Rehoboth Beach. Two years ago, I wrote a blog post about our beach vacation at Marielyst in Denmark that I blended with my reflections about present-day collaborative science, which many of our readers liked a lot. Admittedly, there wasn’t all that much time for the beach ever since, but we managed to squeeze in a weekend at the Delaware beaches two weeks ago. Two years after my Marielyst post, here is what the beach told me about science in 2015. Continue reading
