title: Screening for novel PAX3 polymorphisms and risks of spina bifida.
abstract: BACKGROUND
  PAX3 plays an important role in mammalian embryonic development. Known mutations in PAX3 are etiologically associated with Waardenburg syndrome and syndromic neural tube defects (NTDs). Mutations in the murine homologue, pax3, are responsible for the phenotype of splotch mice, in which nullizygotes are 100% penetrant for NTDs.
  
  
  METHODS
  The study sample included 74 infants with spina bifida (cases) and 87 nonmalformed infant controls. The conserved paired-box domain as well as the upstream genomic region of PAX3 were subjected to resequencing and those identified SNPs were evaluated as haplotypes. The associations of haplotypes for selected gene regions and the risks of spina bifida were further studied.
  
  
  RESULTS
  Nineteen SNPs were observed; 15 observed in controls had been submitted to the National Center for Biotechnology Information (NCBI) database with allele frequencies. The PAX3 gene variant T-1186C (rs16863657) and its related haplotype, TCTCCGCCC of nine SNPs, were found to be associated with an increased risk of spina bifida, with an OR of 3.5 (95% CI: 1.2-10.0) among Hispanic Whites.
  
  
  CONCLUSIONS
  Our analyses indicated that PAX3 SNPs were not strong risk factors for human spina bifida. However, additional follow-up of the PAX3 gene variant T-1186C (rs16863657) and its related haplotype, TCTCCGCCC, may be important in other populations.
authors.affiliation: Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, Texas 77030, and Children's Hospital Oakland Research Institute, CA, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhu
authors.forename: Shu
authors.initials: S
authors.lastname: Wen
authors.forename: Cecile
authors.initials: C
authors.lastname: Laurent
authors.forename: Gary M
authors.initials: GM
authors.lastname: Shaw
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Lammer
authors.forename: Richard H
authors.initials: RH
authors.lastname: Finnell
mesh_terms: D016022:Case-Control Studies; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008957:Models, Genetic; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D016135:Spinal Dysraphism / Q000175:diagnosis / Q000235:genetics*
chemical_list: D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors