Two novel mutations of PTEN gene in Japanese patients with Cowden syndrome

Cowden syndrome (CS), also known as multiple hamartoma syndrome, is an autosomal dominant cancer syndrome associated with high risk of breast and thyroid cancer. In three unrelated Japanese CS patients, three PTEN germline mutations were identified, including two novel ones: 589A  T, resulting in Lys197Stop, and 219-222delAAGA. We also detected a previously reported mutation: 697C  T, resulting in Arg233Stop. Reports from Western countries have indicated that approximately two-thirds of mutations are found in exons 5, 7, and 8, which is almost the same frequency as found in Japanese CS. No genotype–phenotype correlations have been found in CS patients from 21 Japanese families. © 2003 Wiley-Liss, Inc.