title: Novel single nucleotide polymorphisms in the superoxide dismutase 1 and 2 genes among children with myelomeningocele.
abstract: OBJECTIVE
  Excessive oxidative stress has been demonstrated as a mechanism for neural tube defects (NTDs). The current exploratory study sought to examine sequence variations in the superoxide dismutase 1 (SOD1) and 2 (SOD2) genes in patients with myelomeningocele and to identify variants altering risk for myelomeningocele.
  
  
  METHODS
  We sequenced deoxyribonucleic acid from 96 patients with myelomeningocele. The 11 exons were amplified by polymerase chain reaction, and the products were sequenced with the Sanger method. Results were compared with reference sequences (NM_000454, NM_000636, and NM_001024466) obtained from University of California Santa Cruz Genome Browser. Observed alleles that differed from the reference sequences were considered novel variants.
  
  
  RESULTS
  We found 1 novel variant and 1 variant only recently described in phase 1 of the 1000 Genomes Project but not yet validated. The novel variant is located in the 3'-untranslated region (UTR) of SOD2 and is present in 2 of 96 patients (1.0% allele frequency). The other variant is located in the 3'-UTR of SOD1 and is present in 2 of 96 patients (1.0% allele frequency). Minor allele frequencies of known single nucleotide polymorphisms were compared with unaffected population controls.
  
  
  CONCLUSIONS
  We identified 1 novel variant and made the second report of an additional variant in the SOD genes studied. The variant located in the 3'-UTR of SOD1 is predicted to alter microribonucleic acid (miRNA) binding. The variant located in the 3'-UTR of SOD2 is predicted to alter 2 miRNA binding sites and potentially affects messenger ribonucleic acid production. We also identified 2 known single-nucleotide polymorphisms that occur in significantly different frequency compared with the unaffected population controls.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, The University of Texas Medical School at Houston, Houston, TX.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Kase
authors.forename: Hope
authors.initials: H
authors.lastname: Northrup
authors.forename: Kit Sing
authors.initials: KS
authors.lastname: Au
mesh_terms: D020413:3' Untranslated Regions; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008591:Meningomyelocele / Q000235:genetics*; D017058:Mexican Americans / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D044465:White People / Q000235:genetics; D000099156:Superoxide Dismutase 2
chemical_list: D020413:3' Untranslated Regions; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C000606290:SOD1 protein, human
keywords: myelomeningocele; single-nucleotide polymorphism; superoxide dismutase