Most of the mutated WPD residues have been considered not to influence or to only partially affect PTEN catalytic activity.14 The somatic p.(Phe90Ser) PTEN mutation has been found in cancer (glioma, endometrium), and had normal phosphatase activity against PIP3 but a reduced ability to bind membrane phospholipids and recruit PTEN for PIP3 signalling.7 The germline c.269T>C, p.(Phe90Ser) PTEN mutation in fibroblasts of our patient produced a stable protein with an unexpected deficit in activity against PI(3,4)P2. This evidence concerns the gene PTEN and cancer.