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.
Tag Archives: GEFS+
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
Mutations in the same residue and phenotypic consequences in SCN1A
The link between a mutation and the corresponding phenotype in genetic epilepsies is sometimes not trivial. Mutations in the same gene can lead to different phenotypes (phenotypic heterogeneity) and different genes can lead to the same phenotype (genetic heterogeneity). These issues appear to be particularly prominent in some forms of seizure disorders. One of the many active research fields in genetics is studying whether environmental factors or other mutations lead to the development of a given syndrome.
Generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI) can be due to the mutations in the same residue of the alpha-subunit of a voltage gated sodium channel encoded by SCN1A. Japanese researches now report in Epilepsia that the interaction with the beta-subunit of the channel rescues the GEFS+ associated mutant A1685V but not A1685D considered to be responsible for SMEI.
It’s a small step up on our understanding of such mutants. Computational analysis suggests that both variants have strong effects. E.g. Polyphen-2 predicts both to be probably damaging. It will still require further research on interactions to assess the differences. Part of this research is carried out in EuroEPINOMICS projects.
