Abstract
Nonsyndromic cleft lip with or without cleft palate (NSCL/P) accounts for 70% of the total number of patients with cleft lip with or without cleft palate (CL/P) and is the most common type of congenital deformity of the craniomaxillofacial region. In this study, whole exome sequencing (WES) and Sanger sequencing were performed on affected members of a Han Chinese family, and a missense variant in the platelet-derived growth factor C (PDGFC) gene (NM_016205: c.G93T: p.Q31H) was identified to be associated with NSCL/P. Bioinformatic studies demonstrated that the amino acid corresponding to this variation is highly conserved in many mammals and leads to a glutamine-to-histidine substitution in an evolutionarily conserved DNA-binding domain. It was found that the expression of PDGFC was significantly decreased in the dental pulp stem cells (DPSCs) of NSCL/P cases, compared to the controls, and that the variant (NM_016205: c.G93T) reduced the expression of PDGFC. In addition, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that Pdgfc deficiency disrupted NSCL/P-related signaling pathways such as the MAPK signaling pathway and cell adhesion molecules. In conclusion, our study identified a missense variant (NM_016205: c.G93T) in exon 1 of PDGFC potentially associated with susceptibility to NSCL/P.