Identification of protein-truncating variants has been a mainstay of mendelian disease gene discovery in the past, and has been similarly fruitful here. However, the evidence suggests that more than half of the 30 genes in which one or more truncating variants was found are not implicated in the causation of mental retardation. Therefore, a small number of truncating variants in a gene found through a genome-scale screen of a large number of disease cases requires careful evaluation and cannot be regarded as strong evidence of disease causation on its own.
