A heterozygous germline mutation of the PTEN/MMAC1 gene in a patient with Cowden disease.

Cowden disease, or multiple hamartoma syndrome, is an autosomal dominant inherited cancer syndrome with a high risk of thyroid and breast cancers. Its susceptibility gene has been mapped to chromosome 10q22-23. Because a newly found tumor suppressor gene, PTEN/MMAC1, often mutated in glioblastoma and in prostatic and breast cancers, has been mapped to the same chromosomal locus, it is suspected that it may be the gene responsible for Cowden disease. germline mutations of the gene have been reported in 4 of 5 families with Cowden disease. We performed a genetic analysis of the PTEN/MMAC1 gene in a sporadically found patient with the disease who had no apparent family history of the disease. We found a germline heterozygous mutation of the PTEN/MMAC1 gene in a patient with Cowden disease. The mutation, a C to T substitution of a single base at codon 130, leads to a formation of stop codon, generating a truncated protein lacking both protein phosphatase signature motif and tensin-like domain. Our finding supports the hypothesis of the PTEN/MMAC1 gene as being responsible for Cowden disease even in a sporadic case.