Germline PTEN mutations in three families with Cowden syndrome

Cowden syndrome (CS) is an autosomal dominant inherited disorder characteri zed by hamartomas in a variety of tissues including the skin, thyroid, brea st, endometrium, and the brain. Individuals with CS are predisposed to deve lopment of malignancy in these organs, especially the breast and the thyroi d. We describe 3 unrelated individuals with CS associated with germline PTE N mutations. While the frameshift (375insTTTA) and the missense (Gly69Arg) mutations reported herein are novel in CS, the nonsense (Arg130stop) mutati on has been described in 2 families with CS and in a single family exhibiti ng both CS and Bannayan-Zonana phenotype.