PTEN and Cowden disease: It has already been reported for another mutant associated with ASD, PTEN H93R, that this mutation caused a significant reduction in activity in vitro and in cells, to approximately 15% of wild type activity in vitro.29 In agreement with our own data, it seems possible that strong but incomplete loss of activity may be related to the observation of ASD symptoms in the absence of some of the more severe phenotypes seen in some patients with Cowden syndrome.