title: Genetic variations in the GLUT3 gene associated with myelomeningocele.
abstract: OBJECTIVE
  Our objectives were to examine the extent of described sequence variation in the glucose transporter 3 (GLUT3) gene in children with myelomeningocele (MM), identify novel variations in the GLUT3 gene in these children, and determine whether these variations may confer a risk of MM.
  
  
  METHODS
  We sequenced the 10 exons of GLUT3, including exon-intron boundaries, on 96 children with MM. Sequencing was performed with Sanger methods and results analyzed with deoxyribonucleic acid analysis software. Frequencies of known single-nucleotide polymorphisms were identified, and those differing from the reference sequence (GRCh37/hg19 assembly) were considered variations.
  
  
  RESULTS
  Six novel and 9 previously described, genetic variations were identified in our population. The novel variations included a large, 83 base pair deletion involving the core promoter region and part of exon 1 (1 of 96 children), and a 2 base pair deletion in the coding sequence of exon 4 (1 of 96 children). The remaining novel variations were located in the introns in the proximity of the splice sites. Novel mutations in GLUT3 were observed among 6.25% of our population. Additionally, the frequency of the rare allele for rs17847972 located in a splice donor site is higher (P < .001) in MM in our population than expected.
  
  
  CONCLUSIONS
  We identified previously undescribed deletions and single-nucleotide variations involving the GLUT3 gene that may be associated with increased susceptibility to MM. Of particular interest, the 2 deletions involve both an important core promoter site and a coding region predicted to have a deleterious effect. The functional significance of these findings is under investigation.
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Medicine, University of Texas Medical School at Houston, Houston, TX. Electronic address: brendan.d.connealy@uth.tmc.edu.
authors.forename: Brendan D
authors.initials: BD
authors.lastname: Connealy
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, University of Texas Medical School at Houston, Houston, TX; Shriners Hospital for Children, Houston, TX.
authors.forename: Hope
authors.initials: H
authors.lastname: Northrup
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, University of Texas Medical School at Houston, Houston, TX.
authors.forename: Kit Sing
authors.initials: KS
authors.lastname: Au
mesh_terms: D005091:Exons; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D051274:Glucose Transporter Type 3 / Q000235:genetics*; D006801:Humans; D008591:Meningomyelocele / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D051274:Glucose Transporter Type 3; C495687:SLC2A3 protein, human
keywords: GLUT3 gene; Sanger sequencing; genetic variations; myelomeningocele