Dravet Syndrome and rare variants in SCN9A

How monogenic is monogenic? Dravet Syndrome is a severe epileptic encephalopathy starting in the first year of life. More than 80% of patients have mutations or deletions in SCN1A, which makes Dravet Syndrome a relatively homogeneous genetic epilepsy. In addition to SCN1A, other genetic risk factors for Dravet Syndrome have been suggested, and current, large-scale studies including EuroEPINOMICS-RES are studying the genetic basis of the minority of Dravet patients negative for SCN1A. A recent paper in Epilepsia now suggests that a significant fraction of patients with Dravet Syndrome also carry rare variants in SCN9A in addition to the mutations in SCN1A. Is a mutation in SCN1A not sufficient to result in Dravet Syndrome, but needs additional genetic modifiers? Continue reading

Seizures beget seizures through splicing in flies

The dynamic genome. Up to 95% of human genes undergo a process called alternative splicing. For these genes, several exons are present, which can be used alternatively or can be omitted. Accordingly, a single pre-mRNA can result in a variety of different proteins with different properties. For key players such as voltage-dependent sodium channels, it is therefore interesting to know which role alternative splicing plays in epilepsy. However, the splicing landscape of human sodium channels is complicated and difficult to investigate. Therefore, a model system is required where simple questions can be asked. A recent study now reveals interesting findings related to sodium channel splicing and seizure in the fruit fly.  Continue reading