PTEN and PTEN hamartoma tumor syndrome: The majority of PTEN missense mutations found in PHTS occur in the phosphatase domain of PTEN (Eng, 2003; Mester and Eng, 2013) and most of these result in full or partial inactivation of PTEN's PIP3 activity (Eng, 2003; Rodríguez-Escudero et al., 2011).