1. ¹Laboratoire de Biochimie Hormonale et Génétique, Hôpital Bichat-Claude Bernard, AP-HP, Faculté de Médecine Paris VII, Paris, France
2. ²Service de Dermatologie, Hôpital Saint-Louis, AP-HP, Faculté de Médecine Paris VII, Paris, France
3. ³Service de Dermatologie, Hôpital Ambroise Paré, AP-HP, Faculté de Médecine Paris-Ile de France Ouest, Boulogne Billancourt, France
4. ⁴Service de Dermatologie, Hôpital Bichat-Claude Bernard, Paris, AP-HP, Faculté de Médecine Paris VII, Paris, France
5. ⁵Service de Dermatologie, Hôpital Henri Mondor, Créteil, AP-HP, Faculté de Médecine Paris XIII, Paris, France
6. ⁶Service de Dermatologie, Hôpital Cochin-Tarnier, Paris, AP-HP, Faculté de Médecine Paris V, Paris, France

Correspondence: Dr N Soufir, Laboratoire de Biochimie Hormonale et Génétique, IFR02, Hôpital Bichat-Claude Bernard, 46 rue Henri Huchard, Paris 75018, France. E-mail: nsoufir@yahoo.com

Received 22 March 2006; Revised 6 July 2006; Accepted 7 July 2006.

Abstract

The patched (PTCH) mutation rate in nevoid basal cell carcinoma syndrome (NBCCS) reported in various studies ranges from 40 to 80%. However, few studies have investigated the role of PTCH in clinical conditions suggesting an inherited predisposition to basal cell carcinoma (BCC), although it has been suggested that PTCH polymorphisms could predispose to multiple BCC (MBCC). In this study, we therefore performed an exhaustive analysis of PTCH (mutations detection and deletion analysis) in 17 patients with the full complement of criteria for NBCCS (14 sporadic and three familial cases), and in 48 patients suspected of having a genetic predisposition to BCC (MBCC and/or age at diagnosis 40 years and/or familial BCC). Eleven new germline alterations of the PTCH gene were characterised in 12 out of 17 patients harbouring the full complement of criteria for the syndrome (70%). These were frameshift mutations in five patients, nonsense mutations in five patients, a small inframe deletion in one patient, and a large germline deletion in another patient. Only one missense mutation (G774R) was found, and this was in a patient affected with MBCC, but without any other NBCCS criterion. We therefore suggest that patients harbouring the full complement of NBCCS criteria should as a priority be screened for PTCH mutations by sequencing, followed by a deletion analysis if no mutation is detected. In other clinical situations that suggest genetic predisposition to BCC, germline mutations of PTCH are not common.