1. ^*Departments of Pathology and Dermatology, Hospital Santa Creu i Sant Pau, Barcelona, Spain;
2. ^†Department of Dermatology, Hospital del Mar, Barcelona, Spain;
3. ^‡Department of Dermatology, Universitat de Lleida, Spain;
4. ^§Department of Dermatology, Hospital Virgen de Aranzazu, San Sebastian, Spain;
5. ^¶Department of Dermatology, Hospital General, Valencia, Spain;
6. ^**Department of Dermatology, Hospital Vall d'Hebron, Barcelona, Spain;
7. ^††Department of Dermatology, Hospital Clinico Universitario, Valencia, Spain;
8. ^‡‡Department of Internal Medecine, Hospital General de Elda, Spain

Correspondence: Dr Xavier MATIAS-GUIU, Department of Pathology, Hospital de la Santa Creu i Sant Pau, Avda Sant Antoni Claret 167, 08025 Barcelona, Spain. Email: xmatiasg@santpau.es

Received 30 August 2001; Revised 16 November 2001; Accepted 26 November 2001.

Abstract

Cowden syndrome is an autosomal dominant genodermatosis, characterized by the presence of multiple hamartomas in the skin, breast, thyroid, gastrointestinal tract, central nervous system, and an increased risk in developing breast and thyroid carcinomas. Over 80 germline mutations of the tumor suppressor gene PTEN, on chromosome 10q23, have been reported in more than 100 unrelated patients and families; however, questions regarding distribution of the mutations in populations from different geographic areas, and phenotypic expression are still unclear. In this study the results are reported of mutation analysis of PTEN in 13 families from Spain and one family of Brazilian origin with Cowden syndrome. PTEN germline mutations were detected in nine of them (64%). Five mutations were located in exon 5, one in exon 6, two in exon 7, and one in exon 8. Four of the mutations were novel. In another case, an identical change had been previously reported as a somatic mutation in an endometrial carcinoma. In one family, the patient presented a de novo mutation, which was not detected in his parents. In five patients, the detection of the PTEN germline mutation confirmed their condition, even in the absence of sufficient criteria to make the clinical diagnosis of Cowden syndrome.