The authors have no conflicts to disclose.
Evaluating rare coding variants as contributing causes to non-syndromic cleft lip and palate
Article first published online: 10 OCT 2012
© 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Special Issue: Variant
Volume 84, Issue 5, pages 496–500, November 2013
How to Cite
Evaluating rare coding variants as contributing causes to non-syndromic cleft lip and palate., .
- Issue published online: 17 OCT 2013
- Article first published online: 10 OCT 2012
- Accepted manuscript online: 14 SEP 2012 08:52AM EST
- Manuscript Revised: 11 SEP 2012
- Manuscript Accepted: 11 SEP 2012
- Manuscript Received: 9 JUL 2012
- NIH. Grant Numbers: R37-DE008559, U01-DE020057
- candidate gene;
- cleft lip;
- cleft palate;
Rare coding variants are a current focus in studies of complex disease. Previously, at least 68 rare coding variants were reported from candidate gene sequencing studies in non-syndromic cleft lip and palate (NSCL/P), a common birth defect. Advances in sequencing technology have now resulted in thousands of sequenced exomes, providing a large resource for comparative genetic studies. We collated rare coding variants reported to contribute to NSCL/P and compared them to variants identified from control exome databases to determine if some might be rare but benign variants. Seventy-one percentage of the variants described as etiologic for NSCL/P were not present in the exome data, suggesting that many likely contribute to disease. Our results strongly support a role for rare variants previously reported in the majority of NSCL/P candidate genes but diminish support for variants in others. However, because clefting is a complex trait it is not possible to be definitive about the role of any particular variant for its risk for NSCL/P.