Association between genes on chromosome 4p16 and non-syndromic oral clefts in four populations

Roxann G. Ingersoll, Jacqueline Hetmanski, Ji Wan Park, M. Daniele Fallin, Iain McIntosh, Yah Huei Wu-Chou, Philip K. Chen, Vincent Yeow, Samuel S. Chong, Felicia Cheah, Jae Woong Sull, Sun Ha Jee, Hong Wang, Tao Wu, Tanda Murray, Shangzhi Huang, Xiaoqian Ye, Ethylin Wang Jabs, Richard Redett, Gerald RaymondAlan F. Scott, Terri H. Beaty

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Isolated cleft lip with or without cleft palate and cleft palate are among the most common human birth defects. Several candidate gene studies on MSX1 have shown significant association between markers in MSX1 and risk of oral clefts, and re-sequencing studies have identified multiple mutations in MSX1 in a small minority of cases, which may account for 1-2% of all isolated oral clefts cases. We explored the 2-Mb region around MSX1, using a marker map of 393 single nucleotide polymorphisms (SNPs) in 297 cleft lip, with or without cleft palate, case-parent trios and 84 cleft palate trios from Maryland, Taiwan, Singapore, and Korea. Both individual markers and haplotypes of two to five SNPs showed several regions yielding statistical evidence for linkage and disequilibrium. Two genes (STK32B and EVC) yielded consistent evidence from cleft lip, with or without cleft palate, trios in all four populations. These two genes plus EVC2 also yielded suggestive evidence for linkage and disequilibrium among cleft palate trios. This analysis suggests that several genes, not just MSX1, in this region may influence risk of oral clefts.

Original languageEnglish (US)
Pages (from-to)726-732
Number of pages7
JournalEuropean Journal of Human Genetics
Issue number6
StatePublished - Jun 2010

Bibliographical note

Funding Information:
We thank all participants and staff members at each institution who contributed data for this project. We also thank the Johns Hopkins SNP Center for carrying out the genotyping. This study was supported by NIH R01-DE-01448 (THB) and NIH R01-DE-013939 (AFS).


  • Chromosome 4p16
  • Cleft lip with or without cleft palate
  • Cleft palate
  • MSX1
  • Oral clefts


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