Exome mining. Trio exome sequencing is both easy and difficult at the same time. If you manage to identify a plausible de novo mutation, the job is pretty much done. However, if no plausible de novo is found, things can become complex very quickly. Some of the known genes for recessive disorders are quite variable and therefore difficult to interpret. Also, we know little about the overall spectrum of the recessive disorders and the plausibility of atypical cases. A recent paper in Clinical Genetics takes a comprehensive approach to the genetic basis of pediatric epilepsies by exome sequencing. The authors include the analysis of recessive and compound heterozygous variants, and they follow up on some of the biomarkers that establish the diagnosis. There are some surprising findings. Continue reading →