Germline mutations of the PTEN/MMAC1 gene in Japanese patients with Cowden disease.

Cowden disease (CD) is an autosomal dominant disorder which confers a high susceptibility to diverse benign and malignant tumors. The PTEN/MMAC1 gene was identified as being responsible for CD, since its germline mutations have been identified in affected individuals in the United States and Europe. We identified three novel germline PTEN mutations, a 2-bp deletion, a 1-bp insertion and a missense mutation, in three of five Japanese patients with CD. The missense mutation resided outside of the region encoding a putative phosphatase domain of the predicted PTEN protein, where previously reported missense mutations in CD patients have been clustered. The present result suggests that a wide range of germline PTEN mutations may play a role in the pathogenesis of CD.