A notable limitation of gene panels targeting known genes is that this approach cannot be used to discover novel genetic diseases; that said, unexpected phenotypes can still be detected, as exemplified by patient 23 who presented with cutaneous vasculitis caused by immune dysregulation associated with Cowden syndrome caused by mutation in PTEN [47, 48]; and patient 28, a female with unclassified autoinflammation and the unexpected finding of the highly penetrant c.391G>A, p.E131K mutation in WAS(Table 3) [31]. This evidence concerns the gene WAS and Cowden disease.