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

TitleExon sequencing of PAX3 and T (brachyury) in cases with spina bifida.
Publication TypeJournal Article
Year of Publication2013
AuthorsAgopian, AJ, Bhalla, AD, Boerwinkle, E, Finnell, RH, Grove, ML, Hixson, JE, Shimmin, LC, Sewda, A, Stuart, C, Zhong, Y, Zhu, H, Mitchell, LE
JournalBirth Defects Res A Clin Mol Teratol
Date Published2013 Sep
KeywordsBase Sequence, Exons, Fetal Proteins, Gene Frequency, Genetic Association Studies, Genetic Variation, Genotype, Humans, Molecular Sequence Data, Odds Ratio, Paired Box Transcription Factors, PAX3 Transcription Factor, Promoter Regions, Genetic, Sequence Analysis, DNA, Spinal Dysraphism, T-Box Domain Proteins, United States

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.

Alternate JournalBirth Defects Res. Part A Clin. Mol. Teratol.
PubMed ID23913553
PubMed Central IDPMC3877942
Grant ListR01 HD039081 / HD / NICHD NIH HHS / United States
R01 HD039195 / HD / NICHD NIH HHS / United States
HD39081 / HD / NICHD NIH HHS / United States
HD39195 / HD / NICHD NIH HHS / United States

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