The above analysis does not necessarily indicate that we can detect causal mutations for a rare Mendelian disease merely by sequencing one subject, and we acknowledge that we did not utilize the true exome-sequencing data. Nevertheless, the results suggest that filtering through a series of steps in ANNOVAR may help drastically reduce the number of candidate genes to a handful of genes that are human-manageable. In this regard, one could imagine that these 20 candidate genes can be sequenced in additional patients affected with Miller syndrome by conventional Sanger sequencing techniques, and the causal gene is likely to be identified directly from these additional sequencing runs.
