A Novel PAX3 Variant in a Chinese Pedigree with Nonsyndromic Cleft Lip With or Without Palate

Objectives: Nonsyndromic cleft lip with or without palate (NSCL/P) is a common congenital orofacial defect, which is associated with severe disruption of orofacial development. The present study was designed to identify potential underlying gene variants in a Chinese pedigree with NSCL/P, in which the proband and the proband's father were affected. Methods: DNA was extracted from the participants' peripheral venous blood, and whole-exome sequencing was performed on the proband and the proband's parents. Results: After filtering, a paired box gene 3 (PAX3) missense variant (c.92C>G_p.Thr31Ser) was identified, which was verified by Sanger sequencing. This variant, which was not present in 113 unrelated healthy individuals or in a Chinese public database, may affect the transcription inhibition domain of the PAX3 protein. Conservation analysis and in silico predictions suggested that this variant may be evolutionarily conserved and potentially deleterious. In addition, it was reported that mice with PAX3 variants show cleft palates. Thus, the PAX3 missense variant (c.92C>G_p.Thr31Ser) is a candidate causative variant in this family. Conclusions: To the best of our knowledge, the present study is the first to report on a PAX3 variant in a pedigree with NSCL/P. The present study further suggests that PAX3 may be associated with CL/P etiology.