Exon sequencing of PAX3 and T (Brachyury) in cases with spina bifida.

Birth defects research. Part A, Clinical and molecular teratology

PubMedID: 23913553

Agopian AJ, Bhalla AD, Boerwinkle E, Finnell RH, Grove ML, Hixson JE, Shimmin LC, Sewda A, Stuart C, Zhong Y, Zhu H, Mitchell LE. Exon sequencing of PAX3 and T (Brachyury) in cases with spina bifida. Birth Defects Res Part A Clin Mol Teratol. 2013;.
BACKGROUND
Based on studies in animals and humans, PAX3 and T (brachyury) are candidate genes for spina bifida. However, neither gene has been definitively identified as a risk factor for this condition.

METHODS
Sanger sequencing was used to identify variants in all PAX3 and T exons and promoter regions in 114 spina bifida cases. For known variants, allele frequencies in cases were compared with those from public databases using unadjusted odds ratios. Novel variants were genotyped in parents and assessed for predicted functional impact.

RESULTS
We identified common variants in PAX3 (n?=?2) and T (n?=?3) for which the allele frequencies in cases were significantly different from those reported in at least one public database. We also identified novel variants in both PAX3 (n?=?11) and T (n?=?1) in spina bifida cases. Several of the novel PAX3 variants are predicted to be highly conserved and/or impact gene function or expression.

CONCLUSION
These studies provide some evidence that common variants of PAX3 and T are associated with spina bifida. Rare and novel variants in these genes were also identified in affected individuals. However, additional studies will be required to determine whether these variants influence the risk of spina bifida. Birth Defects Research (Part A), 2013. © 2013 Wiley Periodicals, Inc.