A Novel Mutation of PTCHD3 Identified in a Chinese Family with Basal Cell Nevus Syndrome-associated Odontogenic Keratocysts.

Abstract

Objective: To elucidate the genetic aetiology of basal cell nevus syndrome (BCNS) within a Chinese cohort featuring an affected family.

Methods: The patient's and their parents' peripheral venous blood was collected for high-throughput exon sequencing. Tools such as Mutation Taster2 and SIFT were used to predict mutation harmfulness and obtain the most suspected pathogenic mutation. GeneMANIA was employed to construct the protein interaction network between the gene and Hedgehog pathway. SWISS-MODEL was used to simulate the bioinformatics structure changes of the mutant gene and HDOCK was utilised to simulate molecular docking. Finally, the function of this gene mutation was verified by q-PCR.

Results: A novel pathogenic mutation of PTCHD3 was identified. CCDC57 in the Hedgehog pathway was found to interact with PTCHD3 through GeneMANIA. SWISS-MODEL predicted that PTCHD3 mutation would lead to changes in the 3D structure of the protein. HDOCK showed that the binding between PTCHD3 and CCDC57 was significantly reduced. The mutation of PTCHD3 may result in decreased binding ability of PTCHD3 to CCDC57, activate the Hedgehog pathway and lead to the occurrence of the disease. The diagnosis and treatment pathway for clinical discovery of OKC was provided.

Conclusion: A novel pathogenic mutation of PTCHD3 was identified in Chinese BCNS patients. PTCHD3 may play a role in various biological processes mediated by the Hedgehog signalling pathway and is expected to be a new potential therapeutic target.