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