The era of gene retirement. As of 2015, the list of epilepsy genes has shrunk by one. EFHC1, a gene initially proposed to be a monogenic cause of Juvenile Myoclonic Epilepsy, is no longer an epilepsy gene. A recent study in Epilepsia finds that EFHC1 variants initially thought to be pathogenic are found in unaffected controls of the same ancestry. Follow us on one of the most perplexing journeys that modern day neurogenetics has to offer, and the retirement of the first epilepsy gene. Continue reading
Tag Archives: false positive
An inconvenient truth – segregation of monogenic variants in small families
Climate change. In the era of exome and genome sequencing, it might be worthwhile revisiting the merit of family studies in epilepsy research. Seizure disorders are known to have a highly diverse genetic architecture. When singleton studies identify a single, unique gene finding, this discovery usually does not provide much information about the potential causal role of the variant given the high degree of genomic noise. In contrast, family studies are usually considered more robust, as segregation of variants can be traced. Here is the inconvenient truth: unless the family is very large, segregation of possibly monogenic variants adds little information given the vast amount of variants present in our genomes. Continue reading
