Germline Mutations of the PTCH Gene in Families with Odontogenic Keratocysts and Nevoid Basal Cell Carcinoma Syndrome

Abstract

Background/Aims: Odontogenic keratocysts (OKC) are aggressive lesions in the jaws, which can occur as isolated cases or in association with nevoid basal cell carcinoma syndrome (NBCCS). Mutations on PTCH gene have been identified in patients with NBCCS. It was hypothesized that PTCH mutations may be causative in isolated OKC. This study aims to investigate germline mutations of PTCH in families with OKC and NBCCS. Methods: Three Chinese families with OKC and NBCCS were enrolled in the study. The diagnosis was based on examination and medical history. Mutation analysis was performed by amplifying all exons of PTCH and sequencing the products. Results: One family with isolated OKC (family 1) and the other two families with NBCCS were diagnosed. Three novel germline mutations in PTCH were identified, including a missense mutation (p.S1089>P) in family 1, a nonsense mutation (p.Q160X) in family 2 and a de novo mutation (c.768_777delGACAAACTTC) in family 3. Conclusions: It is proposed that isolated OKC can be inherited in an autosomal dominant mode. The results suggest that germline mutations on PTCH can cause isolated OKC, and that the PTCH gene responsible for NBCCS plays an important role in the formation of OKCs even when they are not syndrome-related.