title: Genetic studies of the cystathionine beta-synthase gene and myelomeningocele.
abstract: BACKGROUND
  Among infants born with spina bifida, the most common defect is myelomeningocele (MM). The prevention of MM by maternal periconceptional folic acid (FA) supplementation has been studied extensively. The protective effect provided by FA suggests that the genes involved in folate metabolism, such as cystathionine beta-synthase (CBS), warrant further investigation.
  
  
  METHODS
  This study sequenced the DNA from 96 patients with MM to identify novel potential disease-causing variants across the 17 exons of the CBS gene. The frequencies of known single nucleotide polymorphisms (SNPs) were identified, and sequences that differed from the reference sequences were considered novel variants. Statistical analysis was performed using two-sided Fisher's exact test to compare frequencies of SNPs between groups of patients and the known population frequencies.
  
  
  RESULTS
  We found a new variant in exon 3 in one patient that results in a G/A change subsequently encoding a stop codon. In addition, we found a new variant in the 3'-UTR of exon 17. Allele frequencies for 10 known single nucleotide polymorphisms (SNPs) were determined: rs234706, rs72058776, rs1801181, rs6582281, rs71872941, rs12613, rs706208, rs706209, rs73906420, and rs9982921. Of the remaining 48 known SNPs, all tested DNAs were homozygous for the major allele.
  
  
  CONCLUSIONS
  We identified a previously undescribed variant in exon 3 that encodes a stop codon, thus halting downstream translation of the CBS protein. According to the Human Splicing Finder, the 3'-UTR variant found in exon 17 is predicted to abolish the recognition sites for two splice binding factors, SRp40 and SF2/ASF. The functional significance of the 3'-UTR mutation needs to be investigated.
authors.affiliation: Division of Neonatal-Perinatal Medicine, Department of Pediatrics The University of Texas Medical School at Houston, Houston, Texas 77030, USA.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Tilley
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 / Q000235:genetics; D000328:Adult; D018389:Codon, Nonsense; D003541:Cystathionine beta-Synthase / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008591:Meningomyelocele / Q000208:ethnology / Q000235:genetics*; D017058:Mexican Americans / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D018389:Codon, Nonsense; D003541:Cystathionine beta-Synthase