title: PTCH mutations and deletions in patients with typical nevoid basal cell carcinoma syndrome and in patients with a suspected genetic predisposition to basal cell carcinoma: a French study.
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 < or =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.
authors.affiliation: Laboratoire de Biochimie Hormonale et Génétique, IFR-02, Hôpital Bichat-Claude Bernard, AP-HP, Faculté de Médecine Paris VII, 46 rue Henri Huchard, 75018 Paris, France. nsoufir@yahoo.com
authors.forename: N
authors.initials: N
authors.lastname: Soufir
authors.forename: B
authors.initials: B
authors.lastname: Gerard
authors.forename: M
authors.initials: M
authors.lastname: Portela
authors.forename: A
authors.initials: A
authors.lastname: Brice
authors.forename: M
authors.initials: M
authors.lastname: Liboutet
authors.forename: P
authors.initials: P
authors.lastname: Saiag
authors.forename: V
authors.initials: V
authors.lastname: Descamps
authors.forename: D
authors.initials: D
authors.lastname: Kerob
authors.forename: P
authors.initials: P
authors.lastname: Wolkenstein
authors.forename: I
authors.initials: I
authors.lastname: Gorin
authors.forename: C
authors.initials: C
authors.lastname: Lebbe
authors.forename: N
authors.initials: N
authors.lastname: Dupin
authors.forename: B
authors.initials: B
authors.lastname: Crickx
authors.forename: N
authors.initials: N
authors.lastname: Basset-Seguin
authors.forename: B
authors.initials: B
authors.lastname: Grandchamp
mesh_terms: D001478:Basal Cell Nevus Syndrome / Q000235:genetics*; D002280:Basal Cell Carcinoma / Q000235:genetics*; D005602:France; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006801:Humans; D018895:Microsatellite Repeats; D009154:Mutation; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface