Exon sequencing reveals that missense mutation of PBX1 gene may increase the risk of non-syndromic cleft lip/palate

Objective: Non-syndromic oral cleft (NSOC) is one of the most common multifactorial birth defects. A previous animal study showed PBX1 gene knockout mice consequently exhibited complete cleft lip/palate (CL/P). However, little is known about the association between PBX1 and NSOC in humans. This study investigated the role of the PBX1 gene in NSOC in the Han Chinese population. Methods: In all, 287 NSOCs were recruited for this study. First, exons in the PBX1 gene were sequenced among 50 non-syndromic cleft lip and palate cases to screen for variations by the Sanger sequencing method. Then, we selected four SNPs to replicate among 237 NSOC trios and analyzed the data by usingTDT and parent of origin effect methods. Results: Exon sequencing identified six variants of the PBX1 gene. Among them, four variants were common variants. TDT analysis revealed allele G at rs2275558 and allele T at rs3835581 were over-transmitted in NSCL/P (P=0.039 and 0.038, respectively), which could increase the risk for NSCL/P. Parent of origin effect analysis indicated that allele G at rs2275558 was paternally over-transmitted for NSCL/P (P=0.0091). Conclusion: This is the first report that the PBX1 gene is associated with NSCL/P, which indicates that it is a promising candidate gene for NSCL/P.